ORCID Profile
0000-0001-7554-9717
Current Organisation
University of Adelaide
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Publisher: Wiley
Date: 25-06-2003
DOI: 10.1034/J.1399-302X.2003.00069.X
Abstract: Fusobacterium nucleatum, grown in a chemically defined medium at micro(rel) = 0.5, produced greater cell yields and undetectable levels of intracellular polyglucose (IP) when fructose was substituted for glucose. The utilisation and metabolism of fructose by growing cells was studied and the effect of the energy-yielding amino acids, glutamate, serine, histidine and lysine on cell yield, IP synthesis and acidic end-products was investigated. When F. nucleatum was grown on elevated amino acid levels, IP was synthesised from fructose and amino acids were metabolised to lactate, acetate, butyrate and formate. Under these conditions, IP synthesis was associated with the cells being replete with amino acid-derived energy an observation supported by the absence of IP when the levels of (energy yielding) amino acids were reduced. Compared with fructose, glucose was less efficiently removed from the growth medium and produced less biomass and markedly lower levels of IP during energy-limited growth.
Publisher: Wiley
Date: 10-1992
DOI: 10.1111/J.1399-302X.1992.TB00592.X
Abstract: It has been claimed that most strains of Fusobacterium nucleatum require peptides rather than free amino acids for growth. In contrast, we have shown that, under continuous culture conditions, all strains tested grow in a chemically defined medium (CDM). The purposes of this study were to determine whether resting cells of F. nucleatum could attack unsubstituted peptides and whether growing cells could utilize a peptide fraction prepared from a commercial peptone. Resting cells cleaved all 19 peptides, containing 3-6 residues, and the 4 key energy-yielding amino acids--Glu, His, Ser and Lys--were rapidly taken up. A hydrophilic Casitone fraction, rich in Glu, promoted growth and peptides < 1 kDa were rapidly utilized. The cleaved residues metabolized were those previously shown to limit growth in CDM: Glu, Ser, His and Lys. The endopeptidase activities of Porphyromonas gingivalis would provide the necessary peptides for the growth of F. nucleatum, which may partly explain why these two organisms frequently coexist in periodontally diseased sites.
Publisher: Wiley
Date: 26-11-2010
DOI: 10.1111/J.1600-0765.2010.01320.X
Abstract: The porcine enamel matrix derivative, EMD(®), which is the active component of Emdogain(®), is used widely in periodontics because of its ability to promote the regeneration of soft and hard tissues and to reduce inflammation. Previous studies have used indirect methods to explain its angiogenic and proliferative effects on cells associated with wound healing. In this study we used proteomic techniques to identify proteins in EMD other than amelogenins. Proteins in EMD were separated by two-dimensional gel electrophoresis and were identified using mass spectrometry. Proteomic results were validated by western blot analysis of Emdogain. Fourteen proteins of porcine origin were identified and included the serine and cysteine proteinase inhibitors alpha1-antichymotrypsin and fetuin A, respectively. Alpha1-antichymotrypsin is an acute-phase factor that has been reported to indirectly down-regulate the expression of the gelatinase MMP-9. Fetuin A, a major glycoprotein component of bone and teeth, is a potent inhibitor of ectopic calcification of vascular and soft tissues and has been implicated in both osteogenesis and bone resorption. It also facilitates plasma membrane repair in damaged fibroblasts. EMD contains a number of high-molecular-weight compounds which include the proteinase inhibitors, fetuin A and alpha1-antichymotrypsin.
Publisher: Wiley
Date: 25-06-2014
DOI: 10.1111/IEJ.12301
Abstract: To determine whether clonal ersity within E. faecalis affects biofilm formation when exposed to antimicrobial compounds found in endodontic medicaments and irrigants. Five human isolates of E. faecalis were compared biofilms were grown in microtitre trays in the presence of sodium hypochlorite, calcium hydroxide, chlorhexidine, tetracycline or clindamycin. Biofilms were quantified by staining with crystal violet and optical density determined with a microplate reader. Slime production (an amorphous extracellular matrix comprising polysaccharides, glycoproteins and glycolipids loosely attached to the cell surface) was determined qualitatively by growth on Congo red agar plates. Linear mixed models were used to examine whether medicaments affected biofilm growth of the isolates in the presence of the medicaments or irrigants. Overall, different endodontic antimicrobials significantly altered biofilm growth in E. faecalis isolates. Two E. faecalis isolates significantly (P < 0.0001) increased biofilm formation in the presence of tetracycline and one in the presence of NaOCl (P = 0.018). Qualitatively, slime production also varied between isolates and correlated with biofilm production. When subjected to sub-minimum inhibitory concentration (MIC) levels of antimicrobial compounds found in endodontic medicaments, E. faecalis isolates demonstrated significant clonal variation in their capacity to form biofilms. Interestingly, there was a correlation between slime production and the ability of isolates to form a biofilm in the presence of antimicrobials. The results indicate that isolates of E. faecalis that form biofilms in response to endodontic medicaments may be more likely to survive endodontic treatment.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.ANAEROBE.2007.04.005
Abstract: Fusobacterium nucleatum is a Gram-negative anaerobic organism considered to play an important role in the progression of periodontal disease and is commonly found in clinical infections of other body sites. Apart from its metabolic versatility, its cell-surface properties enable it to attach to epithelial cells, collagen, gingival epithelial cells and other bacterial genera, but not with other Fusobacteria. The development of periodontitis is associated with a rise in pH in the gingival sulcus to around 8.5, and this is thought to occur by the catabolism of proteins supplied by gingival crevicular fluid. F. nucleatum is commonly isolated from diseased sites and has also been shown to survive in root canal systems at pH 9.0 after Ca(OH)(2) treatment. In order to survive hostile environmental conditions, such as nutrient deprivation and fluctuating temperature and pH, bacteria form biofilms, which are usually made up of multi-species co-aggregates. We have grown F. nucleatum in a chemostat at a growth rate consistent with that of oral bacteria in vivo and report that, at a growth pH of 8.2, F. nucleatum co-adheres and forms a homogeneous biofilm. Cell-surface hydrophobicity was determined in planktonic and co-adhering cells to characterise the interfacial interactions associated with the response to pH. Cell-surface hydrophobicity was found to increase at pH 8.2 and this was also associated with a decrease in the levels of intracellular polyglucose (IP) and an observed change in the bacterial cell morphology. To our knowledge, these results represent the first study in which F. nucleatum has been shown to co-adhere and form a biofilm, which may be important in the organism's persistence during the transition from health to disease in vivo.
Publisher: Wiley
Date: 08-01-2019
DOI: 10.1111/AEJ.12334
Abstract: This study investigated the efficacy of Er,Cr:YSGG laser and ultrasonic activated irrigation on eradicating a mixed-species biofilm grown in root canals with complex anatomy. The biofilm was grown over 4-weeks in the root canals of decoronated human mandibular molar teeth. Control roots received no further treatment. The remaining roots were chemomechanically prepared using different irrigating protocols: 4% NaOCl and 15% EDTAC with ultrasonic activated irrigation and laser activated irrigation using power settings of 0.5 W and 0.75 W. Cellular viability was determined using serial plating. One tooth from each group was subjected to qualitative SEM analysis. Quantification by culturing revealed significant differences between control group and all other treatment groups. This study demonstrated that chemomechanical irrigation with laser and ultrasonic activated irrigation significantly reduced the bacterial load from complex root canal systems however, there were no significant differences found between the experimental groups.
Publisher: Wiley
Date: 27-11-2008
DOI: 10.1111/J.1834-7819.2008.00077.X
Abstract: The use of ozone therapy in the treatment of dental caries is equivocal. The aim of this study was to use an in vitro model to determine the effects of prior ozone application to dentine on biofilm formation and to measure any associated reduction in bacteria viability. Twenty dentine discs were bonded to the bases of 5 mL polycarbonate screw top vials. Ten dentine discs were infused with ozone for 40 seconds, 10 s les remained untreated as a control. The vials were filled with nutrient medium, sterilized and placed into the outflow from a continuous chemostat culture of Streptococcus mutans and Lactobacillus acidophilus for four weeks. At the conclusion of the experiment bacterial growth was monitored by taking optical density readings of the growth medium in each vial and the outer surface of the dentine specimens were examined by scanning electron microscopy as shown by SEM analysis. Ozone infusion prevented biofilm formation on all the treated s les while there was substantial biofilm present on the control specimens. While the average optical density of the control specimens was almost twice that of the ozone infused dentine (0.710 for the control with a SD of 0.288 and 0.446 for the ozonated s les with a SD of 0.371), the results were not significant (p > 0.05). This preliminary study has shown that the infusion of ozone into non-carious dentine prevented biofilm formation in vitro from S. mutans and L. acidophilus over a four-week period. The possibility exists that ozone treatment may alter the surface wettability of dentine through reaction with organic constituents.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/1947157
Abstract: The present study examined the cell surface proteome of human periodontal ligament stem cells (PDLSC) compared to human fibroblasts. Cell surface proteins were prelabelled with CyDye before processing to extract the membrane lysates, which were separated using 2D electrophoresis. Selected differentially expressed protein “spots” were identified using Mass spectrometry. Four proteins were selected for validation: CD73, CD90, Annexin A2, and sphingosine kinase 1 previously associated with mesenchymal stem cells. Flow cytometric analysis found that CD73 and CD90 were highly expressed by human PDLSC and gingival fibroblasts but not by keratinocytes, indicating that these antigens could be used as potential markers for distinguishing between mesenchymal cells and epithelial cell populations. Annexin A2 was also found to be expressed at low copy number on the cell surface of human PDLSC and gingival fibroblasts, while human keratinocytes lacked any cell surface expression of Annexin A2. In contrast, sphingosine kinase 1 expression was detected in all the cell types examined using immunocytochemical analysis. These proteomic studies form the foundation to further define the cell surface protein expression profile of PDLSC in order to better characterise this cell population and help develop novel strategies for the purification of this stem cell population.
Publisher: Oxford University Press (OUP)
Date: 06-2000
DOI: 10.1111/J.1574-6968.2000.TB09132.X
Abstract: Fusobacterium nucleatum ATCC 10953 was grown in continuous culture and the atmosphere changed stepwise from nitrogen (anaerobiosis) to a mixture of air: oxygen (40:60). No significant differences in biomass were observed and the baseline low level of superoxide dismutase increased only slightly catalase and peroxidase activities were never detected but the level of NADH oxidase increased more than three-fold when oxygen was introduced into the system. In relation to acidic end-products, the relative proportion of acetate increased while that of butyrate decreased. Due mainly, it would seem, to NADH oxidase activity, the culture maintained a low redox potential (E(h)=-274 mV) even under an atmosphere of 40% oxygen in air and dissolved oxygen was not detected. This may, in part, explain the protective role of F. nucleatum for anaerobes in both biofilm and planktonic phases of aerated, mixed cultures of oral bacteria.
Publisher: Wiley
Date: 23-11-2017
DOI: 10.1111/AEJ.12216
Abstract: This review aims to evaluate the antimicrobial efficacy of calcium hydroxide against endodontic pathogens when used for 7 days or longer. A systematic electronic literature search was performed in the PubMed, Embase and EBSCO Dentistry & Oral Sciences Source databases using appropriate key words to identify investigations written in the English language that examined the association between the contact time of intracanal calcium hydroxide dressing and its antimicrobial properties. There were no exclusions based on study design. The search yielded 6993 publications. After duplicate removal, 5913 publications were identified and 11 studies met the inclusion criteria. Results showed that the antimicrobial effect of calcium hydroxide for contact times ranging between seven and 45 days is comparable. Two studies demonstrated contradictory findings when exposure was extended to more than 45 days. Future studies are warranted to investigate and optimise calcium hydroxide application for longer periods and identify the potential benefits of its use in clinical settings.
Publisher: Springer Science and Business Media LLC
Date: 11-1987
DOI: 10.1007/BF02012940
Publisher: Wiley
Date: 07-1991
DOI: 10.1111/J.1600-0765.1991.TB02069.X
Abstract: The present investigation concerned the effect of chemostat-culture cell-free supernatants of Fusobacterium nucleatum on the growth and synthetic activity of human gingival fibroblasts in vitro. Human gingival fibroblasts were cultured in fetal calf serum supplemented Dulbecco-Vogt medium containing various dilutions of conditioned or unconditioned bacterial culture medium. Cell proliferation was monitored by assessing cell growth over 5 days or incorporation of [3H]-thymidine into DNA. Protein and proteoglycan synthesis were monitored by the incorporation of [3H]-proline and [35S]-sulfate, respectively, into macromolecules. While the conditioned culture medium caused a complete inhibition of cell growth and incorporation of [3H]-thymidine DNA, there was no discernible effect on protein or proteoglycan synthesis. This indicated that the cells remained viable yet unable to ide. Such a view was supported by the observation that the inhibitory effect was reversible upon removal of the conditioned medium. This activity had a molecular size less than 30,000, was heat-stable and nonvolatile. Chemical analysis of the conditioned bacterial culture supernatants indicated that high proportions of butyrate, ammonium, and acetate were present. When these components were added to unconditioned medium and tested, most of the inhibitory activity could be attributed to ammonium and butyrate. Since many bacteria which constitute the subgingival microflora release ammonium and butyrate, a very high concentration of these metabolites may well accumulate. Clearly, the potential for inhibition of fibroblast proliferation has ramifications related to diminished tissue repair following bacterially-induced periodontal destruction.
Publisher: Wiley
Date: 27-04-2009
DOI: 10.1111/J.1600-0765.2008.01132.X
Abstract: Live-animal micro-computed tomography is a new and promising technique that can be used to quantify changes in bone volume for periodontal disease models. The major aim of this study was to develop the methodology of live-animal micro-computed tomography and to determine the effect of a novel secretory phospholipase A2 inhibitor on alveolar bone loss. Periodontitis was induced in mice by oral infection with Porphyromonas gingivalis over a period of 13 wk, and live-animal micro-computed tomography scans were taken at different time-points to determine bone volume changes with disease progression. This enabled conclusions to be made as to when treatment was most likely to be effective. In addition, the model was used to investigate a novel drug, the secretory phospholipase A2 inhibitor, KHO64, and its potential ability to inhibit osteoclast bone resorption and treat periodontitis. The results from live-animal micro-computed tomography scans revealed greater, statistically significant, bone volume loss in diseased mice compared with normal mice (p < 0.05). This corresponded to a larger area from the cemento-enamel junction to the alveolar bone crest, as assessed by stereo imaging (p < 0.001). These techniques can therefore detect and quantify alveolar bone loss. Both methods revealed that KHO64 had no significant effect on the volume of bone resorption. Live-animal micro-computed tomography is a robust, reproducible technique that clearly demonstrates significant time-dependent changes in alveolar bone volume in a small-animal model of periodontitis.
Publisher: Wiley
Date: 09-2004
DOI: 10.1111/J.1834-7819.2004.TB00061.X
Abstract: In recent times, it has been proposed to classify endodontic files as single-use items due to a perceived inability to adequately clean the instruments. The purpose of the present study was to quantify the surface debris on files removed from the manufacturer's packaging, and after cleaning using an ultrasonic bath or a thermal disinfector. Stainless steel and rotary nickel-titanium files were examined after removal from the manufacturer's packaging, after instrumentation in broth-contaminated human teeth, and after various cleaning procedures. The cleaning procedures consisted of either a thermal disinfector cycle, ultrasonication with the files placed in a perforated container or ultrasonication with the files loosely placed in a beaker. The presence of manufacturing debris and biological debris was evaluated using scanning electron microscopy and quantified using image analysis software. The effectiveness of cleaning was not affected by variation in the size or taper of the files when an effective cleaning procedure was used. Cleaning the files in a thermal disinfector or by ultrasonication within a container did not consistently achieve complete removal of biological debris. Placing the files loosely in the ultrasonic bath achieved the most effective cleaning, an average of 98.33 per cent of the file surface area was freed of any biological debris. A conventional cleaning method is capable of effectively removing biological debris from endodontic files. The efficacy of ultrasonic cleaning was impaired when the files were placed within a perforated container.
Publisher: American Society for Microbiology
Date: 15-12-2009
DOI: 10.1128/JVI.01419-09
Abstract: Dengue virus (DENV) pathogenesis is related to the host responses to viral infection within target cells, and therefore, this study assessed intracellular changes in host proteins following DENV infection. Two-dimensional gel electrophoresis and mass spectrometry identified upregulation of the host endoplasmic reticulum (ER) chaperone GRP78 in K562 cells following DENV infection, in the absence of virus-induced cell death. Upregulation of GRP78 in DENV-infected cells was confirmed by immunostaining and confocal microscopy and by Western blot analysis and was also observed in DENV-infected primary monocyte-derived macrophages, a natural target cell type for DENV infection. GRP78 was upregulated in both DENV antigen-positive and -negative cells in the DENV-infected culture, suggesting a bystander effect, with the highest GRP78 levels coincident with high-level DENV antigen production and infectious-virus release. Transfection of target cells to express GRP78 prior to DENV challenge did not affect subsequent DENV infection, but cleavage of GRP78 with the SubAB toxin, during an established DENV infection, yielded a 10- to 100-fold decrease in infectious-virus release, loss of intracellular DENV particles, and a dramatic decrease in intracellular DENV antigen. However, DENV RNA levels were unchanged, indicating normal DENV RNA replication but altered DENV antigen levels in the absence of GRP78. Thus, GRP78 is upregulated by DENV infection and is necessary for DENV antigen production and/or accumulation. This may be a common requirement for viruses such as flaviviruses that depend heavily on the ER for coordinated protein production and processing.
Publisher: Oxford University Press (OUP)
Date: 10-2018
Abstract: Haemophilus influenzae and Streptococcus pneumoniae are known aetiologic agents of chronic otitis media, frequently as a multispecies infection. In this study, we show that the outcome of H. influenzae/S. pneumoniae interactions is dependent on the nutrient source. In continuous culture containing chemically defined media with lactose, S. pneumoniae was non-viable in mono-culture, and in co-culture remained non-viable until 288 h. With glucose, S. pneumoniae became non-viable in mono-culture, but uniquely existed in 3 distinct states in co-culture: parental cells (until 24 h), a dormant state until 336 h and its re-emergence as a non-mucoidal, small colony variant (SCV). The S. pneumoniae SCV was stable and whole genome sequencing showed three major single nucleotide polymorphisms in the SCV cells-cap3A (capsule biosynthesis pathway), fpg (DNA glycosylase of the DNA repair mechanism) and glutamate-5-kinase. Previously, fpg mutants have shown increased mutator rates, permitting bacterial survival against host-generated stresses. Transcriptomics showed these SCV cells up-regulated sugar transporters and toxin/antitoxin systems. An animal model revealed a reduced survival in the lungs and ear by SCV cells. This is the first study documenting the effect of carbon source and the development of a distinct S. pneumoniae cell type during H. influenzae/S. pneumoniae interactions.
Publisher: Mary Ann Liebert Inc
Date: 10-2010
Abstract: Postnatal mesenchymal stem/stromal-like cells (MSCs) including periodontal ligament stem cells (PDLSCs), dental pulp stem cells (DPSCs), and bone marrow stromal cells (BMSCs) are capable of self-renewal and differentiation into multiple mesenchymal cell lineages. Despite their similar expression of MSC-associated and osteoblastic markers, MSCs retain the capacity to generate structures resembling the microenvironments from which they are derived in vivo and represent a promising therapy for the regeneration of complex tissues in the clinical setting. With this in mind, systematic approaches are required to identify the differential protein expression patterns responsible for lineage commitment and mediating the formation of these complex structures. This is the first study to compare the differential proteomic expression profiles of ex vivo-expanded ovine PDLSCs, DPSCs, and BMSCs derived from an in idual donor. The two-dimensional electrophoresis was performed and regulated proteins were identified by liquid chromatography--electrospray-ionization tandem mass spectrometry (MS and MS/MS), database searching, and de novo sequencing. In total, 58 proteins were differentially expressed between at least 2 MSC populations in both sheep, 12 of which were up-regulated in one MSC population relative to the other two. In addition, the regulation of selected proteins was also conserved between equivalent human MSC populations. We anticipate that differential protein expression profiling will provide a basis for elucidating the protein expression patterns and molecular cues that are crucial in specifying the characteristic growth and developmental capacity of dental and non-dental tissue-derived MSC populations. These expression patterns can serve as important tools for the regeneration of particular tissues in future stem cell-based tissue engineering studies using animal models.
Publisher: American Chemical Society (ACS)
Date: 27-01-2021
Publisher: Wiley
Date: 26-04-2004
Publisher: S. Karger AG
Date: 1987
DOI: 10.1159/000261024
Abstract: Paralog reduction, the loss of duplicate genes after whole genome duplication (WGD) is a pervasive process. Whether this loss proceeds gene by gene or through deletion of multi-gene DNA segments is controversial, as is the question of fractionation bias, namely whether one homeologous chromosome is more vulnerable to gene deletion than the other. As a null hypothesis, we first assume deletion events, on either homeolog, excise a geometrically distributed number of genes with unknown mean μ, and a number r of these events overlap to produce deleted runs of length l. There is a fractionation bias 0 ≤ φ ≤ 1 for deletions to fall on one homeolog rather than the other. The parameter r is a random variable with distribution π(·). We simulate the distribution of run lengths l, as well as the underlying π(·), as a function of μ, φ and θ, the proportion of remaining genes in duplicate form. We show how s ling l allows us to estimate μ and φ. The main part of this work is the derivation of a deterministic recurrence to calculate each π(r) as a function of μ, φ and θ. The recurrence for π provides a deeper mathematical understanding of fractionation process than simulations. The parameters μ and φ can be estimated based on run lengths of single-copy regions.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2021
Publisher: American Society for Microbiology
Date: 03-1988
DOI: 10.1128/IAI.56.3.687-692.1988
Abstract: For dental plaque organisms such as Streptococcus sanguis, the ecological importance of the ability to utilize arginine as an energy source has been established in previous studies. The present investigation was undertaken to determine the ability of a strain of S. sanguis to process unsubstituted arginine-containing peptides. The organism was grown under glucose-limited conditions in a chemically defined medium, and peptide was added to washed, resting cells in a pH-stat at pH 7.0. Filtrates taken at appropriate time intervals were assayed for peptide, free amino acids, and metabolites. Irrespective of the position of the arginine residue, all peptides tested were attacked, although those that possessed a C-terminal arginine (including a tetrapeptide) were processed at a faster rate than were those in which arginine was N terminal. However, C-terminal arginine was cleaved only slowly from a peptide containing 24 residues. In each case, most of the released arginine was converted to ornithine via the arginine deiminase pathway. Such peptidase activities appeared to occur at or near the cell surface and were probably constitutive. It was found that the organism grew in chemically defined medium containing arginine that was present solely in the form of a tripeptide, and also that a strain of S. mutans possessed only a limited ability to attack arginine-containing peptides and was unable to utilize the released arginine.
Publisher: Wiley
Date: 12-1987
DOI: 10.1111/J.1399-302X.1987.TB00303.X
Abstract: The extracellular matrix (ECM) of the brain is essential for homeostasis and normal functions, but is rapidly remodelled during acute brain injury alongside the development of an inflammatory response driven by the cytokine interleukin (IL)-1. Whether the ECM regulates IL-1 actions in astrocytes is completely unknown. The aim of this study was to test the hypothesis that cellular attachment to the ECM is a critical mediator of IL-1beta-induced signalling pathways and development of reactive phenotype in astrocytes. Primary rat astrocytes adhered to fibronectin, laminin and fibrillin-1 in an integrin-dependent manner. Attachment to these ECM molecules significantly increased IL-1beta-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and inhibition of RhoA and Rho kinase (ROCK), coincident with loss of focal adhesions and cellular morphological changes. Our data demonstrate that the ECM regulates IL-1 actions in astrocytes via cross-talk mechanisms between ERK1/2 and RhoA/ROCK, which could have important implications in brain inflammatory disorders.
Publisher: Wiley
Date: 06-1991
DOI: 10.1111/J.1834-7819.1991.TB04709.X
Abstract: Continuous culture is a means whereby organisms can be grown at rates approaching those occurring naturally. Moreover, the effect of adding transient excesses of various nutrients to the culture vessel ('pulsing') simulates the effect of dietary challenge on dental plaque organisms. Mixed cultures of Streptococcus mutans T8 and Streptococcus milleri B448 were grown glucose-limited in a chemically defined medium under an atmosphere of 5 per cent carbon dioxide in nitrogen, at a dilution rate of D = 0.1 h-1 and controlled pH of 7.0. The level of arginine in the medium reservoir was adjusted so that Strep. milleri predominated over Strep. mutans in a stable coexistence. After equilibration, the culture vessel was pulsed with various carbohydrates to a final concentration of 5 x 10(-2)mol/L. S les were then taken at regular intervals and differential viable counts of Strep. mutans and Strep. milleri were done on mitissalivarius agar. Results demonstrated that pulsing with glucose, fructose, 'coupling sugar', lactose, xylose and sorbitol gave Strep. mutans a clear ecological advantage. In direct contrast, pulsing with xylitol resulted in a marked antimicrobial effect on Strep. mutans while Strep. milleri was essentially unaffected. This supports recent findings by other workers that uptake of this pentitol by Strep. mutans in batch culture sets up a 'futile cycle', leading to depressed growth or even cell death.
Publisher: Research Square Platform LLC
Date: 07-07-2021
DOI: 10.21203/RS.3.RS-579361/V1
Abstract: Background: The aim of the systematic review was to evaluate the effect of periodontal interventions on the ersity and composition of periodontal microbiota assessed by high throughput sequencing (HTS) metagenomics analysis. Methods: An electronic search of all relevant databases was conducted from database inception to May 2021 by two independent reviewers. All clinical trials that evaluated the effect of periodontal interventions on the gingival microbiota through HTS were selected. The measures of alpha ersity was used as primary outcome richness, Shannon ersity index, and the Chao1 index, whereas relative abundances of bacterial genera was considered as secondary outcome. The Robvis tool was used to assess the risk of bias. Results: Overall, 19 studies were eligible for the systematic review, of which 10 studies were included in the meta-analysis. Periodontal intervention for test group resulted in decrease in Shannon’s ersity, richness and Chao I index as observed from baseline to post-treatment. The most common genera found to increase after periodontal therapy were Rothia, Actinomyces, Streptococcus, Veillonella and Hemophilus and Porphyromonas, Tannerella, Fusobacterium, and Treponema decreased after periodontal therapy . Conclusion: Periodontal interventions may decrease the bacterial ersity and richness and alter the composition of oral microbiota in the short-term. Periodontal microbiota signatures could potentially be used for the assessment of periodontal intervention in the future. Further studies should implement methodological consistency to provide a more quantitative and mechanistic understanding of these approaches.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Public Library of Science (PLoS)
Date: 29-11-2021
DOI: 10.1371/JOURNAL.PONE.0260433
Abstract: Oral microbiome transplantation (OMT) is a novel concept of introducing health-associated oral microbiota into the oral cavity of a diseased patient. The premise is to reverse the state of oral dysbiosis, and restore the ecological balance to maintain a stable homeostasis with the host immune system. This study will assess the effectiveness, feasibility, and safety of OMT using an interdisciplinary approach. To find donors suitable for microbial transplantation, supragingival plaque s les will be collected from 600 healthy participants. Each s le (200μL) will subsequently be examined in two ways: 1) 100μL of the s le will undergo high-throughput 16S rRNA gene licon sequencing and shotgun sequencing to identify the composition and characterisation of a healthy supragingival microbiome, 2) the remaining 100μL of the plaque s le will be mixed with 25% artificial saliva medium and inoculated into a specialised in-vitro flow cell model containing a hydroxyapatite disk. To obtain sufficient donor plaque, the s les would be grown for 14 days and further analysed microscopically and sequenced to examine and confirm the growth and survival of the microbiota. S les with the healthiest microbiota would then be incorporated in a hydrogel delivery vehicle to enable transplantation of the donor oral microbiota. The third step would be to test the effectiveness of OMT in caries and periodontitis animal models for efficacy and safety for the treatment of oral diseases. If OMTs are found to be successful, it can form a new treatment method for common oral diseases such as dental caries and periodontitis. OMTs may have the potential to modulate the oral microbiota and shift the ecological imbalances to a healthier state.
Publisher: Kare Publishing
Date: 2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8RA02145G
Abstract: 2-Methyl-2-oxazoline plasma polymerized silver nanoparticles containing coatings are not toxic towards mouse kidney derived stem cells (mKSCs) and regulate mKSCs differentiation.
Publisher: American Society for Microbiology
Date: 02-2015
DOI: 10.1128/IAI.02702-14
Abstract: An undetermined feature of Staphylococcus aureus pathogenesis is its persistence and then relapse of disease. This has been explained by its switch to alternative lifestyles, mainly as biofilm or small-colony variants (SCVs). Studying the native characteristics of SCVs has been problematic due to their reversion to the parental lifestyle. We have observed that for a number of S. aureus strains as they switch to an SCV lifestyle, there is the formation of an extracellular matrix. We focused our analysis on one strain, WCH-SK2. For bacterial survival in the host, the combination of low nutrients and the prolonged time frame forms a stress that selects for a specific cell type from the population. In this context, we used steady-state growth conditions with low nutrients and a controlled low growth rate for a prolonged time and with methylglyoxal. These conditions induced S. aureus WCH-SK2 into a stable SCV cell type the cells did not revert after subculturing. Analysis revealed these cells possessed a metabolic and surface profile that was different from those of previously described SCVs or biofilm cells. The extracellular matrix was protein and extracellular DNA but not polysaccharide. The SCV cells induced expression of certain surface proteins (such as Ebh) and synthesis of lantibiotics while downregulating factors that stimulate the immune response (leucocidin, capsule, and carotenoid). Our data reveal cell heterogeneity within an S. aureus population and under conditions that resemble long-term survival in the host have identified a previously unnoticed S. aureus cell type with a distinctive metabolic and molecular profile.
Publisher: Wiley
Date: 04-02-2022
Abstract: There is a globally increasing demand for medically implanted devices, partly spurred by an aging population. In parallel, there is a proportionate increase in implant associated infection. Much focus has been directed toward the development of techniques to fabricate nanostructured antimicrobial biomaterials to mitigate infection. The present study investigates the interaction of the fungal pathogen Candida albicans with an antimicrobial surface bearing nanoscale protrusions. C. albicans cells were observed to be affected by cell wall stress, which impeded its ability to switch to a hyphal phenotype. There are significant differences in the expression of C. albicans virulence‐associated genes between the untreated and nanostructured surfaces. To determine whether the observed inhibition of C. albicans would also sensitize it to antifungal drugs, a culture is established for 3 days on the nanostructured surface before being treated with the antifungal drug hotericin B. The drug was able to kill all cells on the nanostructured surface at sub‐clinical concentrations, while remaining ineffective against cultures grown on a smooth control surface. These findings may eventually prove to be impactful in the clinic, as clinicians may be able to reduce antifungal drug dosages and minimize the effects of drug associated toxicity.
Publisher: Microbiology Society
Date: 2007
DOI: 10.1099/MIC.0.2006/001040-0
Abstract: Fusobacterium nucleatum is a saccharolytic Gram-negative anaerobic organism believed to play an important role in the microbial succession associated with the development of periodontal disease. Its genome contains niche-specific genes shared with the other inhabitants of dental plaque, which may help to explain its ability to survive and grow in the changing environmental conditions experienced in the gingival sulcus during the transition from health to disease. The pH of the gingival sulcus increases during the development of periodontitis and this is thought to occur by the metabolism of nutrients supplied by gingival crevicular fluid. In comparison with other plaque inhabitants, F. nucleatum has the greatest ability to neutralize acidic environments. The differential expression of soluble cytoplasmic proteins induced by acidic (pH 6.4) or basic (pH 7.4 and 7.8) conditions, during long-term anaerobic growth in a chemostat, was identified by two-dimensional gel electrophoresis and image analysis software. Twenty-two proteins, found to have altered expression in response to external pH, were identified by tryptic digestion and mass spectrometry. Eight differentially expressed proteins associated with increased energy (ATP) production via the 2-oxoglutarate and Embden-Meyerhof pathways appeared to be directed towards either cellular biosynthesis or the maintenance of internal homeostasis. Overall, these results represent the first proteomic investigation of F. nucleatum and the identification of gene products which may be important in the organism's persistence during the transition from health to disease in vivo.
Publisher: Springer Science and Business Media LLC
Date: 1990
DOI: 10.1007/BF02094018
Publisher: Microbiology Society
Date: 07-1998
DOI: 10.1099/00221287-144-7-1807
Abstract: The properties of an aminopeptidase (AP) from Fusobacterium nucleatum were studied in view of the fact that this organism, along with other Gram-negative anaerobes involved in periodontal diseases, survives in the subgingival environment by obtaining energy via the fermentation of a small number of peptide-derived amino acids. The AP was found to be cell-associated and was isolated from disrupted chemostat-grown cells. It was purified by (NH 4 ) 2 SO 4 fractionation, two column chromatographic steps and IEF. The enzyme was found to have a molecular mass of 54 kDa, a pl of 5.1, a pH optimum between 7.5 and 8.0 and, using Leu-Ala as substrate, it gave K m and V max values of 0.66 mM and 0.12 μmol min -1 mg -1 , respectively. No complete homology was found between the N-terminal sequence of the first 20 amino acids (MDXKXYVDLKERFLRYVKFN.) and any other published sequence, but residues 8--20 gave a 62% match with residues 9--21 of an AP from Haemophilus influenzae. The enzyme was inactivated by chelating agents, bestatin, p-hydroxymercuribenzoate and some heavy metals. Cobalt ions restored EDTA-inactivated activity but did not reverse inhibition by 1,10-phenanthroline. In addition, bestatin and 1, 10-phenanthroline had an inhibitory effect on the batch growth of F. nucleatum in a complex medium in which peptidase activities would be nutritionally essential. No such inhibition was observed in a chemically defined medium in which growth was not dependent upon peptidase activities. The peptidase described in this paper therefore appears to be a cobalt-activated metallo-AP which, together with other peptidases, is considered to be important in the survival of F. nucleatum in the subgingival environment of the mouth.
Publisher: Wiley
Date: 04-1995
DOI: 10.1111/J.1399-302X.1995.TB00130.X
Abstract: Grown in a chemically defined medium containing glucose at a dilution rate of D = 0.065 h-1, Fusobacterium nucleatum D212B-2 produced large amounts of intracellular polyglucose. Aliquots of this culture were starved by anaerobic incubation at 37 degrees C and at various times, assayed for intracellular polyglucose content and viability. This protocol was repeated using cells grown under the same conditions in a chemically defined medium, a medium lacking carbohydrate and in which the organism produced no intracellular polyglucose. Both cultures had 50% survival time values of about 1.5 h and were not eliminated even after 32 h of starvation. It was, therefore concluded that starvation-survival is not influenced by intracellular polyglucose. Starvation-survival was also determined for cells grown in a chemically defined medium at D = 0.048 h-1 and D = 0.12 h-1. The faster-grown cells had a 50% survival time of 3.8 h but were completely eliminated after 8-16 h of starvation. In contrast, slower-grown cells had a 50% survival time of 1.5 h but were not completely eliminated after 32 h of starvation. This illustrates the importance of cell history and technique standardization in comparing the starvation-survival of different organisms.
Publisher: Wiley
Date: 08-1991
DOI: 10.1111/J.1399-302X.1991.TB00486.X
Abstract: Fusobacterium nucleatum ATCC 10953, a type strain of one of the newly proposed subspecies of this group of organisms, was grown anaerobically in continuous culture in a chemically defined medium. Its response to conditions of varying pH, nutritional environment, and imposed growth rate were then examined. The organism failed to grow at pH 7.8 but grew at pH 5.8, although the cell yield was greatly reduced. At pH 6.8 the cell yield was halved and less than 50% of available glucose was consumed. The optimum growth pH was around 7.4 when the culture appeared to be limited for both glucose and the amino acids glutamate, histidine and serine. Some intracellular polyglucose (IP) was produced and acetate, butyrate and ammonia were the major fermentation end-products, as they were under all growth conditions tested. Increasing the available glucose or amino acids did not alter cell numbers but the amount of IP was greatly increased. When glucose was omitted from the medium, the cell yield was halved and the culture then became limited for lysine as well as for glutamate, histidine and serine. Growth rate had little overall effect on the organism's physiology and the maximum growth rate at pH 7.4 was 0.20 h-1, a doubling time of 3.5 h. Glucose was thus channelled into stable IP synthesis only when the growth limitation imposed by lack of fermentable amino acids was relieved. The metabolism of IP and the ability to obtain carbon and energy from a variety of substrates may explain why F. nucleatum is one of the most commonly detected organisms in subgingival dental plaque.
Publisher: Wiley
Date: 23-01-2023
Abstract: Dental caries is a major disease associated with the proliferation of acidogenic bacterial species such as Streptococcus mutans that are part of the commensal microbiota of the mouth. Silver nanoparticles (AgNPs) are attractive antibacterial agents as they target multiple sites in bacteria which reduces antimicrobial resistance. In this study, we synthesised stable, highly positively charged AgNPs capped with branched PEI (BPEI‐AgNPs) and characterized them using UV–vis absorption, transmission electron microscopy (TEM), the size of which were approximately 7.5 nm. The antibacterial activity and anti‐biofilm capacity of BPEI‐AgNPs was investigated against cariogenic bacteria. Our results demonstrated that BPEI‐AgNPs are potent clinical oral antiseptics. The cytotoxicity of the BPEI‐AgNPs was also studied against two mammalian cell lines. The results indicated that BPEI‐AgNPs were non‐cytotoxic and were safer than commercially used dental antiseptics. We conclude that the BPEI‐AgNPs are safe for oral clinical application and are an effective oral antimicrobial agent.
Publisher: Elsevier BV
Date: 11-2016
DOI: 10.1016/J.JCIS.2016.08.003
Abstract: Silver nanoparticles (AgNPs) have emerged as a powerful weapon against antibiotic resistant microorganisms. However, most conventional AgNPs syntheses require the use of hazardous chemicals and generate toxic organic waste. Hence, in recent year's, plant derived and biomolecule based synthetics have has gained much attention. Cacao has been used for years for its medicinal benefits and contains a powerful reducing agent - oxalic acid. We hypothesized that, due to the presence of oxalic acid, cacao extract is capable of reducing silver nitrate (AgNO3) to produce AgNPs. In this study, AgNPs were synthesized by using natural cacao extract as a reducing and stabilizing agent. The reaction temperature, time and reactant molarity were varied to optimize the synthesis yield. UV-visible spectroscopy (UV-vis), dynamic light scattering (DLS) and transmission electron microscopy (TEM) characterization demonstrated that the synthesized AgNPs were spherical particles ranging in size from 35 to 42.5nm. The synthesized AgNPs showed significant antibacterial activity against clinically relevant pathogens such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus epidermidis. Importantly, these green AgNPs are not cytotoxic to human dermal fibroblasts (HDFs) at concentrations below 32μg/ml. We conclude that cacao-based synthesis is a reproducible and sustainable method for the generation of stable antimicrobial silver nanoparticles with low cytotoxicity to human cells. The AgNPs synthesized in this work have promising properties for applications in the biomedical field.
Publisher: Wiley
Date: 19-05-2016
Publisher: Elsevier BV
Date: 04-1998
Abstract: Fusobacterium nucleatum is a Gram-negative anaerobe, found in a number of different areas of human and animal bodies as part of the resident microbiota. However, it also appears to be involved in polymicrobial infections in such sites. It occurs in the oral cavity where it is a prominent member of various bacterial consortia associated with periodontal diseases. Like most fusobacteria, it derives energy via the fermentation of amino acids which it can obtain through the dissimilation of small peptides. However, the role of simple carbohydrates, such as glucose, in its growth and metabolism are not well understood. Accordingly, the aim of the present study was to study the behaviour ofF. nucleatum grown anaerobically in continuous culture in two different chemically-defined media (CDM) one containing only amino acids as the energy source, the other containing glucose as the predominant energy provider. At various dilution rates the culture were assayed for dry weight, intracellular polyglucose (IP) content, residual amino acids and glucose and acidic metabolic end-products. In the carbohydrate-free CDM the acidic end-products were a constant acetate : butyrate : formate of 1.5 : 1 : 0.4. The values of Y(max)amino acids, maximum yield of bacteria per mol of amino acids consumed, for two strains were estimated to be 15.2 and 18.6 g dry wt/mol, respectively. Them(amino acids), maintenance energy requirement for growth on amino acids, for the two strains was 0.81 and 0.94 mmol/g dry wt/h, respectively. Growth of one strain in the glucose-based CDM gave an estimated Y(max)glucose of 67.2 and an m(glucose) of 0.38 the acidic end-products were a fairly constant acetate : butyrate : formate : lactate of 0.7 : 1 : 0.3 : 2.5. Only at low growth rates, and then only in small amount, was IP produced in this medium. Overall, it was concluded that the occurrence of F. nucleatum in widely-differing oral niches may be explained, at least in part, by its metabolic versatility.
Publisher: Wiley
Date: 06-02-2018
DOI: 10.1111/ADJ.12582
Abstract: Calcium hydroxide is a common endodontic medicament and has an antimicrobial effect by increasing the localized pH within the root canal. However, Enterococcus faecalis has shown some resistance to calcium hydroxide. A flow cell apparatus was used to grow an E. faecalis biofilm on dentine discs. Following 4 weeks growth in Todd Hewitt Broth, flow cells were exposed to either a rapid or slow increase to pH 11.5 or 12.5. Cellular viability was determined using serial plating and the number of colony-forming units was normalized against the cellular protein content. Scanning electron microscopy was carried out to qualitatively observe the effects of the different rates of pH increase. A significant difference in viability between the pH rapid and slow groups was not shown in this study. Compared with pH 11.5 solutions, pH 12.5 solutions were more effective at killing bacteria although some E. faecalis still survived. Enterococcus faecalis did not adapt and develop a greater resistance to high pH following a slow rise in pH compared with a rapid rise in pH. As expected, pH 12.5 was more effective in reducing bacterial numbers compared with pH 11.5 although E. faecalis was not completely eliminated.
Publisher: Wiley
Date: 12-2005
DOI: 10.1111/J.1834-7819.2005.TB00367.X
Abstract: Diamine silver fluoride (Ag(NH3)2F), referred to as AgF, has been used to reduce the incidence of caries in primary dentitions but has been limited by the associated staining of both teeth and restorative materials. The application of potassium iodide (KI), following AgF prevents staining but its effects on the ability of AgF to reduce caries are not known. The aim of this study was to develop an in vitro model that would provide an indication of the permeability of demineralized dentine to Streptococcus mutans after treatment of the dentine with AgF followed by KI. Forty dentine discs were bonded to the base of forty 5mL polycarbonate screw top vials (that had had their bases removed), filled with nutrient medium, sterilized and placed into a continuous culture of S. mutans. S les were ided into four groups as follows: 10 s les of demineralized dentine as a control, 10 s les of demineralized dentine treated with AgF/KI, 10 s les of demineralized dentine treated with KI and 10 s les of demineralized dentine treated with AgF. After two weeks the optical density of the growth medium chambers was measured to determine bacterial penetration and growth. Cultures were plated out to determine migration through the discs by S. mutans. S. mutans migrated through all dentine discs. However, the s les treated with AgF and AgF/KI had significantly lower optical densities than the corresponding controls. The range of optical densities was least amongst demineralized s les treated with AgF/KI. Under the conditions of this study, treatment of demineralized dentine discs with AgF followed by KI allowed the penetration of S. mutans. Based on optical density measurements, the treatment resulted in significantly fewer microorganisms being present subjacent to the discs treated with AgF and KI than the control discs at the end of the experimental period.
Publisher: Wiley
Date: 20-02-2009
DOI: 10.1111/J.1600-0765.2008.01108.X
Abstract: Periodontitis is an infective disease caused predominantly by gram-negative anerobes. The host inflammatory response to these bacteria causes alveolar bone loss, which characterizes periodontitis. Omega-3 polyunsaturated fatty acids have recognized anti-inflammatory effects their oxygenated derivatives are key mediators in reducing inflammation. In this study we tested the hypothesis that dietary supplementation with tuna fish oil rich in the n-3 polyunsaturated fatty acid, docosahexaenoic acid, would reduce alveolar bone loss in mice inoculated with periodontopathic bacteria. Adult mice were fed experimental diets containing either 10% tuna oil or Sunola oil for 57 d. After 14 d, 35 mice on each diet were inoculated orally with Porphyromonas gingivalis, with a mixture of P. gingivalis and Fusobacterium nucleatum, with carboxymethylcellulose or remained untreated. The mice were killed, and soft tissue biopsies from the oral cavity of treated mice were used to determine the polyunsaturated fatty acid concentrations. The maxilla was removed, stained and digitally imaged to assess bone loss around the upper molars. n-3 polyunsaturated fatty acid levels were significantly higher in oral soft tissues of mice fed tuna oil compared with the control group. Mice fed tuna oil and inoculated with P. gingivalis or with the combination of F. nucleatum and P. gingivalis exhibited 72% and 54% less alveolar bone loss respectively, compared with the treatment control group. Alveolar bone loss was inversely related to n-3 polyunsaturated fatty acid tissue levels. In conclusion, fish oil dietary supplementation may have potential benefits as a host modulatory agent in the prevention and/or adjunctive management of periodontitis.
Publisher: Wiley
Date: 02-03-2018
DOI: 10.1111/ADJ.12580
Abstract: Many studies have investigated the effectiveness of root canal irrigants and medicaments against Enterococcus faecalis. The aim of this study was to compare the efficacy of commonly used medicaments against E. faecalis cultured as a biofilm on dentine substrate. An E. faecalis biofilm was established on human dentine slices using a continuous flow cell. Each test medicament (Ledermix, Ca(OH) Sodium hypochlorite achieved total bacterial elimination. Ledermix and Odontopaste had no significant effect on the E. faecalis biofilm. Ca(OH) Sodium hypochlorite remains the gold standard for bacterial elimination in root canal therapy. However, Ca(OH)
Publisher: Wiley
Date: 09-2007
DOI: 10.1111/J.1834-7819.2007.TB00487.X
Abstract: There are a number of studies citing the primary reason for replacing auto cure glass ionomer cements was due to recurrent caries. The purpose of this study was to use an in vitro model to measure caries at the dentine restoration interface of bonded composite resin and auto cure glass ionomer cement restorations and to measure the amount of surface degradation occurring in the restorative materials. Specimens of auto cure glass ionomer cements (Riva Fast, Fuji IX Fast, Ketac Molar Quick and Fuji VII) and bonded composite resin restorations (Ice, SDI) were placed separately at the dentino-enamel junction of 10 recently extracted human third molar teeth, disinfected and placed into the overflow from a continuous culture of S. mutans for two weeks. Restorations were sectioned and prepared for scanning electron microscopy (SEM) and electron probe microanalysis (EPMA). Restoration tooth interfaces were photographed and the distance from the surface of the teeth to the surface of the restorations measured. EPMA of percentage weights of calcium, phosphorous and fluoride were made outwards from the restoration surface 130pm at a depth of 10 microm below the surface of the dentine. There were significant differences between the surface heights of composite resin, auto cure glass ionomer cements compared to teeth surfaces. Percentage weights of calcium and phosphorus levels were similar to non-demineralized dentine in the auto cure glass ionomer cement s les but there were significant reductions in mineral content of dentine adjacent to bonded composite resin restorations. Fluoride levels were mixed. This study shows that placing a bonded composite resin restoration into dentine affords little protection to the surrounding tooth from caries attack although insignificant degradation of the restorative surface occurs. Placing a glass ionomer cement restoration into dentine protects the surrounding tooth from caries but degradation of the restoration surface occurs.
Publisher: Wiley
Date: 03-2007
DOI: 10.1111/J.1834-7819.2007.TB00460.X
Abstract: The application of diamine silver fluoride (Ag(NH3)2F) and potassium iodide (KI) to demineralized dentine has been shown to inhibit the growth of Streptococcus mutans. The purpose of this study was to observe the differences between demineralized and non-demineralized dentine treated with AgF/KI. Thirty-five dentine discs were bonded to the bases of 5 mL polycarbonate screw top vials which were filled with nutrient medium, sterilized and placed into the overflow from a continuous culture of S. mutans. S les were ided as follows: 10 s les of demineralized dentine 10 s les of demineralized dentine treated with AgF/KI 5 s les of non-demineralized dentine and 10 s les of non-demineralized dentine treated with AgF/KI. Following two weeks connected to the Chemostat, an electron probe microanalysis (EPMA) of percentage weights and penetration depths of calcium, phosphorous silver and fluoride was conducted. Bacterial growth was monitored by taking optical density readings of the growth medium in each vial and outer surfaces of the specimens were examined by scanning electron microscopy (SEM). AgF/KI treatment of demineralized and non-demineralized dentine prevented biofilm formation and reduced further demineralization by S. mutans. AgF/KI treatment of demineralized dentine was more effective in reducing dentine breakdown and the growth of S. mutans. Significantly higher levels of silver and fluoride were deposited within demineralized dentine. A topical treatment with AgF/KI on dentine reduced in vitro caries development and inhibited surface biofilm formation. Reduction of in vitro caries development and viability of S. mutans was more pronounced on the dentine s les that had been demineralized prior to the application of
Publisher: Frontiers Media SA
Date: 28-02-2020
Publisher: Wiley
Date: 04-2016
DOI: 10.1111/IEJ.12447
Abstract: To establish the antibacterial efficacy of low concentrations of sodium hypochlorite with and without Er,Cr:YSGG laser activation on Enterococcus faecalis biofilms in extracted teeth. The root canals of 96 decoronated single-rooted extracted human teeth were prepared to a size 40, 0.06 taper 1 mm beyond the apex. They were mounted within a flow cell, which was sterilized before pumping a nutrient media through the root canals. The flow cell was inoculated with E. faecalis (ATCC 700802) and cultivated for 4 weeks. The root-ends were sealed, and the roots were then subjected to one of six treatment groups: group 1: syringe irrigation (SI) with saline (control) using a 27 -gauge Monoject needle 1 mm from the apex for 2 min group 2: as for group 1 but with 1% NaOCl group 3: as for group 1 but with 4% NaOCl group 4: 0.5% NaOCl irrigation for 15 s followed by laser-activated irrigation (LAI) with four 15-s cycles replenishing the irrigant between cycles group 5: as for group 4 but with 1% NaOCl as the irrigant group 6: as for group 4 but with 4% NaOCl as the irrigant. Following treatment, teeth were crushed and viable bacteria were quantitated by serial dilution and plating. The colony-forming unit values were compared between groups using one-way anova and Tukey-adjusted post hoc tests. A two-tailed P value of <0.05 was considered statistically significant. The mean number of cells recovered from the 1% NaOCl SI group was significantly higher than that from the 4% NaOCl LAI group (P = 0.02). Within the limitations of this laboratory study, low-powered (0.5 W) Er,Cr:YSGG laser activation did not improve the antibacterial effect of low concentrations of sodium hypochlorite.
Publisher: American Society for Microbiology
Date: 06-1986
DOI: 10.1128/IAI.52.3.897-901.1986
Abstract: The coexistence of bacteria in natural environments can often be explained in terms of competition for a growth-limiting substrate(s), and the outcome of such competition depends upon relevant growth parameters such as substrate affinity and yield. Dental plaque bacteria are frequently carbon and energy limited. Growth parameters for seven oral Streptococcus species and one Actinomyces viscosus strain were estimated under glucose-limited conditions in continuous culture. In all strains, mixed-acid fermentation occurred at low growth rates, while amounts of lactate increased at higher growth rates. Two important growth parameters, mumax and Y glucose, were very similar in the two serotype c Streptococcus mutans strains (T8 and Ingbritt), one of the serotype d/g Streptococcus mutans strains (OMZ65), and the two Streptococcus milleri strains (699B3 and B448). Two other serotype d/g S. mutans strains (KIR and B13) were ergent from this group and had lower mumax values and a lower Y glucose. The maintenance energy coefficients were lower in the S. mutans serotype c strains, and the highest values were observed in the S. milleri strains. While A. viscosus had a lower mumax, its lower maintenance rate and significantly higher yield indicate that it deals much more efficiently with glucose than do the streptococci. The most striking feature of amino acid utilization was that arginine was completely consumed by S. milleri strains similarly, A. viscosus used up all available asparagine as did one of the S. milleri strains at faster growth rates. It is suggested that the ability of strains of S. milleri and S. sanguis to utilize arginine in addition to carbohydrate as a source of energy may explain why such organisms increase in proportion in the plaque of subjects consuming diets almost devoid of fermentable carbohydrate.
Publisher: Wiley
Date: 04-1991
DOI: 10.1111/J.1399-302X.1991.TB00454.X
Abstract: The binding of a number of unsubstituted peptides to Streptococcus sanguis and Streptococcus mutans and their subsequent degradation by such cells were examined. Peptides were added to cell suspensions prepared from glucose-limited growth in a chemostat and, at appropriate time intervals, cell-free filtrates were analyzed for peptides and their constituent amino acid residues by high-pressure liquid chromatography techniques. The results indicated that peptide hydrophobicity plays a limited role in peptide binding, but that charge and chain-length are probably important. In S. sanguis, carboxypeptidase activity rapidly released C-terminal arginine (Arg) this amino acid was less rapidly released from the N-terminus but a number of other residues were also released by aminopeptidase activity. When Arg is buried in the peptide, the rate of its release depends upon the number and type of residues between it and the N-terminus. In contrast, S. mutans possessed only weak peptidase activities. The nature of its peptidase activities indicates that S. sanguis can obtain the metabolically important Arg from a variety of peptides.
Publisher: MDPI AG
Date: 27-06-2023
DOI: 10.3390/PHARMACEUTICS15071837
Abstract: Dental caries is a common and costly multifactorial biofilm disease caused by cariogenic bacteria that ferment carbohydrates to lactic acid, demineralizing the inorganic component of teeth. Therefore, low pH (pH 4.5) is a characteristic signal of the localised carious environment, compared to a healthy oral pH range (6.8 to 7.4). The development of pH-responsive delivery systems that release antibacterial agents in response to low pH has gained attention as a targeted therapy for dental caries. Release is triggered by high levels of acidogenic species and their reduction may select for the establishment of health-associated biofilm communities. Moreover, drug efficacy can be lified by the modification of the delivery system to target adhesion to the plaque biofilm to extend the retention time of antimicrobial agents in the oral cavity. In this review, recent developments of different pH-responsive nanocarriers and their biofilm targeting mechanisms are discussed. This review critically discusses the current state of the art and innovations in the development and use of smart delivery materials for dental caries treatment. The authors’ views for the future of the field are also presented.
Publisher: Wiley
Date: 04-1990
DOI: 10.1111/J.1399-302X.1990.TB00230.X
Abstract: Our previous studies indicated that Arginine (Arg) plays a key nutritional role in Streptococcus sanguis P4A7 and that this organism can grow on whole casein as the sole nitrogen source. Its protease activities were therefore studied after glucose-limited continuous culture in a chemically-defined medium with either free amino acids or casein as the nitrogen source. Both culture supernatant and cell-associated endopeptidase (EP) and exopeptidase (amino-AP and carboxy-CP) activities were determined. Growth rate (mu) had little effect on EP, 75% of which was consistently in culture supernatants AP and CP both decreased as mu was increased and both were predominantly cell-associated. At high growth pH, EP was substantially increased while AP and CP activities were optimal at pH 7. The most striking nutritional effect occurred under nitrogen limitation (glucose excess) when EP and AP were greatly increased and CP greatly decreased. It was concluded that S. sanguis is well equipped to scavenge its environment for Arg under a wide range of growth conditions.
Publisher: MDPI AG
Date: 06-03-2018
Publisher: MDPI AG
Date: 17-07-2021
Abstract: The metal ion release characteristics and biocompatibility of meta-based materials are key factors that influence their use in orthodontics. Although stainless steel-based alloys have gained much interest and use due to their mechanical properties and cost, they are prone to localised attack after prolonged exposure to the hostile oral environment. Metal ions may induce cellular toxicity at high dosages. To circumvent these issues, orthodontic brackets were coated with a functional nano-thin layer of plasma polymer and further immobilised with enantiomers of tryptophan. Analysis of the physicochemical properties confirmed the presence of functional coatings on the surface of the brackets. The quantification of metal ion release using mass spectrometry proved that plasma functionalisation could minimise metal ion release from orthodontic brackets. Furthermore, the biocompatibility of the brackets has been improved after functionalisation. These findings demonstrate that plasma polymer facilitated surface functionalisation of orthodontic brackets is a promising approach to reducing metal toxicity without impacting their bulk properties.
Publisher: Royal Society of Chemistry (RSC)
Date: 2019
DOI: 10.1039/C9NA00211A
Abstract: The core-in-cage structure of ultra-small AuNPs can be used to define their functions without compromising their size and surface functionalities.
Publisher: Oxford University Press (OUP)
Date: 10-1986
Publisher: Wiley
Date: 04-09-2014
DOI: 10.1111/AEJ.12073
Abstract: Enterococcus faecalis is often involved in the aetiology of apical periodontitis after endodontic treatment. This project aimed to establish, on dentine in vitro, a multi-species biofilm containing E. faecalis, and to determine if the organism had an increased resistance to sodium hypochlorite compared with an axenic biofilm. Biofilms were established on dentine discs in flow cells with either E. faecalis alone (axenic) or together with Fusobacterium nucleatum and Streptococcus sanguinis. Following treatment with either 0.9% sodium hypochlorite or saline, the viability of E. faecalis was determined by serial plating and qualitative analysis was performed by scanning electron microscopy and confocal laser scanning microscopy. Viable counts indicated that 0.9% NaOCl is highly effective against E. faecalis grown alone and as part of a multi-species biofilm (P = 0.0005 and P = 0.001, respectively). No significant difference in its survival in the two biofilm types was found (P = 0.8276).
Publisher: Wiley
Date: 09-2004
Publisher: American Chemical Society (ACS)
Date: 22-12-2021
Abstract: Silver-based nano-antibiotics are rapidly developing as promising alternatives to conventional antibiotics. Ideally, to remain potent against a wide range of drug-resistant and anaerobic bacteria, silver-based nano-antibiotics should easily penetrate through the bacterial cell walls and actively release silver ions. In this study, highly monodispersed, ultrasmall (<3 nm), polycationic silver nanoclusters (pAgNCs) are designed and synthesized for the elimination of a range of common Gram-negative and Gram-positive pathogens and their corresponding established and matured biofilms, including those composed of multiple species. The pAgNCs also show greatly enhanced antibacterial efficacy against anaerobic bacteria such as
Publisher: MDPI AG
Date: 05-07-2018
DOI: 10.3390/NANO8070496
Publisher: Wiley
Date: 11-12-2018
DOI: 10.1111/JCPE.12838
Abstract: This study investigated the role of Lactobacillus rhamnosus GG (LGG) on bone loss and local and systemic inflammation in an in vivo mouse model of experimental periodontitis (PD). Experimental PD was induced in mice by oral inoculation with Porphyromonas gingivalis and Fusobacterium nucleatum over a period of 44 days. The probiotic LGG was administered via oral inoculation or oral gavage prior to, and during disease induction. The antimicrobial activity of LGG on the inoculum was also tested. Alveolar bone levels and gingival tissue changes were assessed using in vivo microcomputed tomography and histological analysis. Serum levels of mouse homologues for IL-8 were measured using multiplex assays. Pre-treatment with probiotics either via oral gavage or via oral inoculation significantly reduced bone loss (p < .0001) and gingival inflammation (p < .0001) when compared with PD group. Oral gavage treatment group had significantly less tartrate-resistant acid phosphatase positive cells (p < .02) then PD group. LGG showed no antimicrobial activity against P. gingivalis and F. nucleatum. Lactobacillus rhamnosus GG effectively suppresses bone loss in a mouse model of induced PD irrespective of the mode of administration.
Publisher: Microbiology Society
Date: 02-2002
DOI: 10.1099/00221287-148-2-467
Abstract: The authors compared the differences in tolerance to oxygen of the anaerobic periodontopathic bacteria Fusobacterium nucleatum and Porphyromonas gingivalis , and explored the possibility that F. nucleatum might be able to support the growth of P. gingivalis in aerated and CO 2 -depleted environments. Both micro-organisms were grown as monocultures and in co-culture in the presence and absence of CO 2 and under different aerated conditions using a continuous culture system. At steady state, viable counts were performed and the activities of the enzymes superoxide dismutase and NADH oxidase eroxidase were assayed in P. gingivalis . In co-culture, F. nucleatum was able to support the growth of P. gingivalis in aerated and CO 2 -depleted environments in which P. gingivalis , as a monoculture, was not able to survive. F. nucleatum not only appeared to have a much higher tolerance to oxygen than P. gingivalis , but a significant increase in its numbers occurred under moderately oxygenated conditions. F. nucleatum might have an additional indirect role in dental plaque maturation, contributing to the reducing conditions necessary for the survival of P. gingivalis and possibly other anaerobes less tolerant to oxygen. Additionally, F. nucleatum is able to generate a capnophilic environment essential for the growth of P. gingivalis .
Publisher: Wiley
Date: 16-04-2018
DOI: 10.1111/ADJ.12604
Abstract: Tooth discolouration could occur due to bacterial contamination in traumatized teeth. Hydrogen peroxide is the commonly used bleaching agent. However, due to concerns over safety, alternative bleaching regimes such as sodium perborate (S) and thiourea-hydrogen peroxide (T) have been investigated. Apices resected and pulp extirpated 99 premolars were ided into two groups. Group 1 and 2 was injected with blood and blood/bacteria, stored anaerobically for 35 days. The two groups were treated by bleaching with water, S or T. Teeth were rebleached after 7 days. Colourimetric evaluation was assessed using digital imaging, CasMatch standardization and CIE L*a*b colour system preoperatively, 35 days of staining and 7 and 14 of bleaching. A linear mixed model with fixed effects of time, group and bleach was used to examine colour difference. Blood-stained teeth were significantly redder and darker on day 35 compared with blood/bacteria-stained teeth. After bleaching, blood-stained teeth retained significant redness compared with blood/bacteria-stained teeth using either S or T. T produced a significantly whiter shade in both the groups after 14 days. Blood-stained teeth were significantly darker and red compared with blood/bacteria-stained teeth. T bleaching regime was more effective than S.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.JOEN.2017.08.025
Abstract: Extracellular material (ECM) surrounding Enterococcus faecalis may play a role in increasing resistance to environmental stresses. Our aim was to determine ECM levels in response to subminimal inhibitory concentrations of sodium hypochlorite (sub-MIC/NaOCl) or anaerobic growth and determine the impact on biofilm development. From 37 E. faecalis clinical strains, 19 were selected according to their biofilm-producing ability by using a crystal violet biofilm assay: 10 strong, 4 intermediate, and 5 non-biofilm producers. Biofilm assays were subsequently performed on all strains when subjected to sub-MIC/NaOCl. All strains were evaluated for ECM production under aerobic and anaerobic conditions and with sub-MIC/NaOCl. ECM production was assessed by using scanning electron microscopy. Double-blinded independent assessors were used to score levels of ECM production. The esp gene was detected by using polymerase chain reaction. Gelatinase activity was determined by using Todd-Hewitt and gelatin agar. In aerobic conditions, ECM was expressed in all strains. In the presence of sub-MIC/NaOCl, of the 10 strong biofilm producers, 5 increased their ECM production, and 4 showed increased biofilm growth. Two strains had less ECM production and showed decreased biofilm growth. One isolate demonstrated no observable changes. Most non-biofilm producers demonstrated no observable differences in ECM production, although 1 strain increased biofilm growth. ECM production in anaerobic conditions was highly variable. The esp gene (n = 15) and gelatinase activity (n = 7) were evident among the isolates. Clonal ersity among strains of E. faecalis suggests that some strong biofilm producers can upregulate ECM production and increase biofilm growth in response to sub-MIC/NaOCl.
Publisher: Public Library of Science (PLoS)
Date: 25-03-2015
Publisher: Springer Science and Business Media LLC
Date: 03-09-2012
Abstract: The Gram negative anaerobe Fusobacterium nucleatum has been implicated in the aetiology of periodontal diseases. Although frequently isolated from healthy dental plaque, its numbers and proportion increase in plaque associated with disease. One of the significant physico-chemical changes in the diseased gingival sulcus is increased environmental pH. When grown under controlled conditions in our laboratory, F. nucleatum subspecies polymorphum formed mono-culture biofilms when cultured at pH 8.2. Biofilm formation is a survival strategy for bacteria, often associated with altered physiology and increased virulence. A proteomic approach was used to understand the phenotypic changes in F. nucleatum cells associated with alkaline induced biofilms. The proteomic based identification of significantly altered proteins was verified where possible using additional methods including quantitative real-time PCR (qRT-PCR), enzyme assay, acidic end-product analysis, intracellular polyglucose assay and Western blotting. Of 421 proteins detected on two-dimensional electrophoresis gels, spot densities of 54 proteins varied significantly ( p 0.05) in F. nucleatum cultured at pH 8.2 compared to growth at pH 7.4. Proteins that were differentially produced in biofilm cells were associated with the functional classes metabolic enzymes, transport, stress response and hypothetical proteins. Our results suggest that biofilm cells were more metabolically efficient than planktonic cells as changes to amino acid and glucose metabolism generated additional energy needed for survival in a sub-optimal environment. The intracellular concentration of stress response proteins including heat shock protein GroEL and recombinational protein RecA increased markedly in the alkaline environment. A significant finding was the increased abundance of an adhesin, Fusobacterial outer membrane protein A (FomA). This surface protein is known for its capacity to bind to a vast number of bacterial species and human epithelial cells and its increased abundance was associated with biofilm formation. This investigation identified a number of proteins that were significantly altered by F. nucleatum in response to alkaline conditions similar to those reported in diseased periodontal pockets. The results provide insight into the adaptive mechanisms used by F. nucleatum biofilms in response to pH increase in the host environment.
Publisher: Elsevier BV
Date: 1984
DOI: 10.1016/0003-9969(84)90119-5
Abstract: As a preliminary to measuring the hydrophobicity of continuous-culture cells, batch-grown cells of a number of Streptococcus mutans strains were tested for their ability to adhere to hexadecane. The hydrophobic properties of such cells were markedly affected by experimental variables such as the composition of the growth medium and the buffer in which the cells were subsequently suspended. For ex le, the replacement of glucose by fructose in a chemically-defined growth medium (CDM) increased cell hydrophobicity. Strep. mutans B13 and Streptococcus milleri B448 were separately grown glucose-limited in the CDM at various dilution rates from D = 0.04 h-1 to D = 0.7 h-1, corresponding to mean generation times of 17 and 1 h. Slow-growing cells of both strains were more hydrophobic than fast-growing cells, which, in conjunction with previous studies, supports the suggestion that hydrophobic bonding may play a role in bacterial adherence.
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D1MA00444A
Abstract: 3D printing provides numerous opportunities for designing tissue engineering constructs with intricate porosity, geometry and favourable mechanical properties and has the potential to revolutionize medical treatments.
Publisher: Microbiology Society
Date: 06-2010
Abstract: Fusobacterium nucleatum is a Gram-negative anaerobic organism that plays a central role in the development of periodontal diseases. The progression of periodontitis is associated with a rise in pH of the gingival sulcus which promotes the growth and expression of virulence factors by periodontopathic bacteria. We have previously reported that the expression of specific cytoplasmic proteins is altered by a shift in growth pH. In the present study we have compared cell envelope protein expression of F. nucleatum during chemostat growth at pH 7.2 and 7.8. From a total of 176 proteins resolved from the cell envelope, 15 were found to have altered expression in response to an increase in growth pH and were identified by MS. Upregulated proteins included an outer membrane porin which has been identified as playing a role in virulence, a periplasmic chaperone which assists in the folding of outer membrane proteins, and a transporter thought to be involved with iron uptake. Proteins downregulated at pH 7.8 were consistent with our previous findings that the bacterium reduces its catabolism of energy-yielding substrates in favour of energy-storage pathways. Among the downregulated proteins, two transporters which are involved in the uptake of C4 dicarboxylates and phosphate were identified. A putative protease and an enzyme associated with the metabolism of glutamate were also identified. A high proportion of the cell envelope proteins suggested by these data to play a role in the organism's response to alkaline growth pH may have arisen by lateral gene transfer. This would support the hypothesis that genes that provide an ability to adapt to the changing conditions of the oral environment may be readily shared between oral bacteria.
Publisher: Wiley
Date: 16-07-2012
DOI: 10.1111/J.1747-4477.2012.00366.X
Abstract: The effectiveness of sonic activation, laser activation and syringe irrigation of 4% sodium hypochlorite in removing an Enterococcus faecalis biofilm was compared. Biofilms were grown in extracted human single rooted teeth using a flow cell apparatus. After 4 weeks' growth, teeth were subjected to each treatment using 4% sodium hypochlorite and radicular dentinal surfaces of the root canals were analysed by scanning electron microscopy. Results showed that sonic activation and syringe irrigation with sodium hypochlorite showed reduced numbers of bacterial cells on the radicular dentine but were not effective in eliminating E. faecalis in the dentinal tubules. Laser activation of sodium hypochlorite resulted in clean dentine walls and undetectable levels of bacteria within dentinal tubules. Qualitatively, sonic or laser activation of 4% NaOCl resulted in greater bacterial reduction compared with syringe irrigation, with laser activation producing the greatest overall reduction.
Publisher: Public Library of Science (PLoS)
Date: 02-02-2017
Publisher: American Chemical Society (ACS)
Date: 14-10-2022
DOI: 10.1021/ACSBIOMATERIALS.2C00540
Abstract: Titanium and its alloys are frequently the biomaterial of choice for dental implant applications. Although titanium dental implants have been utilized for decades, there are yet unresolved issues pertaining to implant failure. Dental implant failure can arise either through wear and fatigue of the implant itself or peri-implant disease and subsequent host inflammation. In the present report, we provide a comprehensive review of titanium and its alloys in the context of dental implant material, and how surface properties influence the rate of bacterial colonization and peri-implant disease. Details are provided on the various periodontal pathogens implicated in peri-implantitis, their adhesive behavior, and how this relationship is governed by the implant surface properties. Issues of osteointegration and immunomodulation are also discussed in relation to titanium dental implants. Some impediments in the commercial translation for a novel titanium-based dental implant from "bench to bedside" are discussed. Numerous in vitro studies on novel materials, processing techniques, and methodologies performed on dental implants have been highlighted. The present report review that comprehensively compares the in vitro , in vivo , and clinical studies of titanium and its alloys for dental implants.
Publisher: Oxford University Press (OUP)
Date: 10-2002
DOI: 10.1111/J.1574-6968.2002.TB11392.X
Abstract: Fusobacterium nucleatum is a Gram-negative anaerobe that has been implicated in the aetiology of several diseases including periodontal diseases. Like other fusobacteria, it derives energy from the fermentation of amino acids and, in resting (non-growing) cells, this enables the organism to transport glucose and synthesise intracellular polyglucose (IP). The continued availability and fermentation of amino acids inhibits IP breakdown. We have grown F. nucleatum in continuous culture in a chemically defined medium under amino acid limitation and determined the fate of glucose during growth at steady state and during transient increases in the concentration (pulses) of serine and glutamate. When grown under steady state conditions, IP synthesis dramatically increased at culture pH values of 6.1 and 7.8 and appeared to be a result of cell stress. IP synthesis also increased when the culture was pulsed with serine or glutamate but was rapidly metabolised as the added amino acids were depleted. These results may help to explain the role of IP synthesis in response to environmental stress.
Publisher: American Society for Microbiology
Date: 15-07-2001
DOI: 10.1128/JB.183.14.4142-4148.2001
Abstract: Porphyromonas gingivalis is an asaccharolytic, gram-negative bacterium that relies on the fermentation of amino acids for metabolic energy. When grown in continuous culture in complex medium containing 4 mM (each) free serine, threonine, and arginine, P. gingivalis assimilated mainly glutamate/glutamine, serine, threonine, aspartate/asparagine, and leucine in free and/or peptide form. Serine and threonine were assimilated in approximately equal amounts in free and peptide form. We characterized serine transport in this bacterium by measuring uptake of the radiolabeled amino acid in washed cells of P. gingivalis energized with a tetrapeptide not containing serine. Serine was transported by a single system with an affinity constant for transport ( K t ) of 24 μM that was competitively inhibited by threonine. Serine transport was dependent on sodium ion concentration in the suspending buffer, and the addition of the ionophore gramicidin caused the inhibition of serine uptake. Together these data indicate that serine transport was sodium ion-motive force driven. A P. gingivalis gene potentially encoding a serine transporter was identified by sequence similarity to an Escherichia coli serine transporter (SstT). This P. gingivalis gene, designated sstT, was inactivated by insertion of a Bacteroides tetQ gene, producing the mutant W50ST. The mutant was unable to transport serine, confirming the presence of a single serine transporter in this bacterium under these growth conditions. The transport of serine by P. gingivalis was dependent on the presence of free cysteine in the suspension buffer. Other reducing agents were unable to stimulate serine uptake. These data show that P. gingivalis assimilates free serine and threonine from culture media via a cysteine-activated, sodium ion-motive force-driven serine/threonine transporter.
Publisher: MDPI AG
Date: 17-02-2023
DOI: 10.3390/ANTIBIOTICS12020406
Abstract: The ability of Staphylococcus aureus to colonise different niches across the human body is linked to an adaptable metabolic capability, as well as its ability to persist within specific tissues despite adverse conditions. In many cases, as S. aureus proliferates within an anatomical niche, there is an associated pathology. The immune response, together with medical interventions such as antibiotics, often removes the S. aureus cells that are causing this disease. However, a common issue in S. aureus infections is a relapse of disease. Within infected tissue, S. aureus exists as a population of cells, and it adopts a ersity of cell types. In evolutionary biology, the concept of “bet-hedging” has established that even in positive conditions, there are members that arise within a population that would be present as non-beneficial, but if those conditions change, these traits could allow survival. For S. aureus, some of these cells within an infection have a reduced fitness, are not rapidly proliferating or are the cause of an active host response and disease, but these do remain even after the disease seems to have been cleared. This is true for persistence against immune responses but also as a continual presence in spite of antibiotic treatment. We propose that the constant arousal of suboptimal populations at any timepoint is a key strategy for S. aureus long-term infection and survival. Thus, understanding the molecular basis for this feature could be instrumental to combat persistent infections.
No related grants have been discovered for Peter Zilm.