ORCID Profile
0000-0003-0180-7837
Current Organisations
CNRS Délégation Languedoc-Roussillon
,
CSIRO Australian Manufacturing and Materials Precinct
,
CSIRO
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Publisher: Springer Science and Business Media LLC
Date: 25-09-2020
DOI: 10.1038/S41598-020-72478-6
Abstract: Inspired by the interesting natural antimicrobial properties of honey, biohybrid composite materials containing a low-fouling polymer hydrogel network and an encapsulated antimicrobial peroxide-producing enzyme have been developed. These synergistically combine both passive and active mechanisms for reducing microbial bacterial colonization. The mechanical properties of these materials were assessed using compressive mechanical analysis, which revealed these hydrogels possessed tunable mechanical properties with Young’s moduli ranging from 5 to 500 kPa. The long-term enzymatic activities of these materials were also assessed over a 1-month period using colorimetric assays. Finally, the passive low-fouling properties and active antimicrobial activity against a leading opportunistic pathogen, Staphylococcus epidermidis , were confirmed using bacterial cell counting and bacterial adhesion assays. This study resulted in non-adhesive substrate-permeable antimicrobial materials, which could reduce the viability of planktonic bacteria by greater than 7 logs. It is envisaged these new biohybrid materials will be important for reducing bacterial adherence in a range of industrial applications.
Publisher: American Chemical Society (ACS)
Date: 10-11-2015
Publisher: IEEE
Date: 02-2014
Publisher: American Chemical Society (ACS)
Date: 09-11-2017
Abstract: Antimicrobial polymers appear as a promising alternative to tackle the current development of bacterial resistance against conventional antibiotics as they rely on bacterial membrane disruption. This study investigates the effect of segmentation of hydrophobic and cationic functionalities on antimicrobial polymers over their selectivity between bacteria and mammalian cells. Using RAFT technology, statistical, diblock, and highly segmented multiblock copolymers were synthesized in a controlled manner. Polymers were analyzed by HPLC, and the segmentation was found to have a significant influence on their overall hydrophobicity. In addition, the amount of incorporated cationic comonomer was varied to yield a small library of bioactive macromolecules. The antimicrobial properties of these compounds were probed against pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis), and their biocompatibility was tested using hemolysis and erythrocyte aggregation assays, as well as mammalian cell viability assays. In all cases, diblock and multiblock copolymers were found to outperform statistical copolymers, and for polymers with a low content of cationic comonomer, the multiblock showed a tremendously increased selectivity for P. aeruginosa and S. epidermidis compared to its statistical and diblock analogue. This work highlights the remarkable effect of segmentation on both the physical properties of the materials as well as their interaction with biological systems. Due to the outstanding selectivity of multiblock copolymers toward certain bacteria strains, the presented materials are a promising platform for the treatment of infections and a valuable tool to combat antimicrobial resistance.
Publisher: CSIRO Publishing
Date: 2020
DOI: 10.1071/CH19544
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.BIOMATERIALS.2019.119249
Abstract: Intracellular persistence of bacteria represents a clinical challenge as bacteria can thrive in an environment protected from antibiotics and immune responses. Novel targeting strategies are critical in tackling antibiotic resistant infections. Synthetic antimicrobial peptides (SAMPs) are interesting candidates as they exhibit a very high antimicrobial activity. We first compared the activity of a library of ammonium and guanidinium polymers with different sequences (statistical, tetrablock and diblock) synthesized by RAFT polymerization against methicillin-resistant S. aureus (MRSA) and methicillin-sensitive strains (MSSA). As the guanidinium SAMPs were the most potent, they were used to treat intracellular S. aureus in keratinocytes. The diblock structure was the most active, reducing the amount of intracellular MSSA and MRSA by two-fold. We present here a potential treatment for intracellular, multi-drug resistant bacteria, using a simple and scalable strategy.
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8CS00508G
Abstract: Zwitterionic polymers, including poly holytes and polybetaines, are polymers with both positive and negative charges incorporated into their structure.
Publisher: Royal Society of Chemistry (RSC)
Date: 2014
DOI: 10.1039/C4PY00652F
Abstract: We report the use of RAFT polymerization to obtain eight cationic methacrylate polymers bearing amine or guanidine pendant groups, while varying the R- and Z-RAFT end-groups.
Publisher: MDPI AG
Date: 08-04-2022
DOI: 10.3390/SU14084425
Abstract: Plastic waste (PW) is one of the most rapid-growing waste streams in municipal solid waste all over the world. India has become a global player in the plastic value chain. Despite low consumption, domestic generation and imports create a significant burden on the overall waste management system, which requires in-depth understanding of the scenario and pathways that can mitigate the crisis. Although Indian researchers have widely researched technology-related issues in academic papers, a substantial knowledge gap exists in understanding the problem’s depth and possible solutions. This review article focuses on current plastic production, consumption, and waste generation in India. This review article mainly analyzes data and information regarding Indian PW management and highlights some critical issues such as reverse supply chain, effective PW management, source-specific recovery, and PW rules in India. Comprehensively, this review will help to identify implementable strategies for policymakers and research opportunities for future researchers in holistic PW management and recycling in India, focusing on the circular economy and sustainable development goals.
Publisher: Wiley
Date: 16-08-2020
Publisher: American Chemical Society (ACS)
Date: 11-02-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2021
DOI: 10.1039/D0CS00986E
Abstract: Macromolecular entities, such as polymers, peptides, proteins, and hybrid materials thereof, are herein reviewed as promising antibiofilm agents.
Publisher: American Chemical Society (ACS)
Date: 14-06-2019
Abstract: One of the most important traits of pathogenic microbial biofilms is their high tolerance to conventional antimicrobial agents, which is partially due to the presence of metabolically inactive and transiently resistant persister cells. Here, we use guanine-rich DNA structures known as G-quadruplexes (G4s) coupled with the β-lactam antibiotic, oxacillin (OX), and loaded with an iron-containing protoporphyrin IX (hemin), as OXG4/hemin complex biofilm-specific antibiotic agents. By coupling the OX to the G4, to form an OXG4/hemin complex, the diffusion of the OX was facilitated into the biofilm. Further, by utilizing the known oxidizing behavior (peroxidase-mimicking) of the G4/hemin complex, the entire system was found to be highly effectively against
Publisher: American Chemical Society (ACS)
Date: 31-01-2014
DOI: 10.1021/AC403735N
Abstract: This study compares three common laboratory methods, size-exclusion chromatography (SEC), (1)H nuclear magnetic resonance (NMR), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), to determine the molecular weight of oligomeric cationic copolymers. The potential bias for each method was examined across a series of polymers that varied in molecular weight and cationic character (both choice of cation (amine versus guanidine) and relative proportion present). SEC was found to be the least accurate, overestimating Mn by an average of 140%, owing to the lack of appropriate cationic standards available, and the complexity involved in estimating the hydrodynamic volume of copolymers. MALDI-TOF approximated Mn well for the highly monodisperse (Đ < 1.1), low molecular weight (degree of polymerization (DP) <50) species but appeared unsuitable for the largest polymers in the series due to the mass bias associated with the technique. (1)H NMR was found to most accurately estimate Mn in this study, differing to theoretical values by only 5.2%. (1)H NMR end-group analysis is therefore an inexpensive and facile, primary quantitative method to estimate the molecular weight of oliogomeric cationic polymethacrylates if suitably distinct end-groups signals are present in the spectrum.
Publisher: Bentham Science Publishers Ltd.
Date: 23-08-2017
Publisher: Springer Science and Business Media LLC
Date: 02-06-2009
DOI: 10.1007/S11064-009-0005-X
Abstract: The incorporation of extra binding groups onto known ligands is a powerful tool for the development of more potent and selective agents at target sites such as the GABA receptors. In the present work we have attempted to build on the activity of the know potent GABA(A) agonist 4-ACP-3-CA and its cis and trans saturated analogues CACP and TACP. We have investigated reactions to add thiol substituents to the alpha,beta-unsaturated system of 4-ACP-3-CA. The reaction was successful with a limited number of thiols but gave products of mixed stereochemistry. The resultant thioether amino acids were screened for activity at human recombinant alpha(1)beta(2) gamma(2L) GABA(A) receptors. The most interesting derivative was the benzylthioether which acted as an antagonist with an IC(50) of 42 microM for the inhibition of a GABA EC(50) dose (50 microM). This study has shown that GABA analogues derived by thiol addition to 4-aminocyclopent-1-enecarboxylic acid display interesting antagonist activity at the alpha(1)beta(2)gamma(2L) GABA(A) receptor.
Publisher: American Chemical Society (ACS)
Date: 07-08-2015
Publisher: SAE International
Date: 23-06-2008
DOI: 10.4271/2008-01-1653
Publisher: CSIRO Publishing
Date: 10-02-2023
DOI: 10.1071/CH22235
Abstract: Women experience numerous forms of discrimination in the workplace, both direct and indirect. Historically, bias against women was institutionalised by organisations and governments to keep women from pursuing long-term careers in science and remain in the home. Although changes to policy have occurred within Australia, societal perceptions around women in science have proven resistant to change, with discrimination continuing even today. Despite the barriers facing them, some women were able to break through and achieve impactful science, proving themselves vital members of the workforce and paving the way for future generations. Herein, we describe four such female chemist trailblazers, Isabel Joy Bear, Enid Plante, Catherine Anne Money and Annabelle Duncan, who each worked at the Council for Scientific and Industrial Research (CSIR) or the subsequent Commonwealth Scientific and Industrial Research Organisation (CSIRO) and helped to shape the face of chemistry in Australia in a male dominated environment.
Publisher: Royal Society of Chemistry (RSC)
Date: 2017
DOI: 10.1039/C7PY00630F
Abstract: A flexible, robust and time-efficient scale-up of multiblock copolymers with low dispersity and high livingness.
Publisher: American Chemical Society (ACS)
Date: 25-10-2013
DOI: 10.1021/BM401128R
Abstract: We have synthesized a series of copolymers containing both positively charged (amine, guanidine) and hydrophobic side chains ( hiphilic antimicrobial peptide mimics). To investigate the structure-activity relationships of these polymers, low polydispersity polymethacrylates of varying but uniform molecular weight and composition were synthesized, using a reversible addition-fragmentation chain transfer (RAFT) approach. In a facile second reaction, pendant amine groups were converted to guanidines, allowing for direct comparison of cation structure on activity and toxicity. The guanidine copolymers were much more active against Staphylococcus epidermidis and Candida albicans compared to the amine analogues. Activity against Staphylococcus epidermidis in the presence of fetal bovine serum was only maintained for guanidine copolymers. Selectivity for bacterial over mammalian cells was assessed using hemolytic and hemagglutination toxicity assays. Guanidine copolymers of low to moderate molecular weight and hydrophobicity had high antimicrobial activity with low toxicity. Optimum properties appear to be a balance between charge density, hydrophobic character, and polymer chain length. In conclusion, a suite of guanidine copolymers has been identified that represent a new class of antimicrobial polymers with high potency and low toxicity.
Publisher: Elsevier BV
Date: 09-2022
Publisher: Cold Spring Harbor Laboratory
Date: 19-11-2021
DOI: 10.1101/2021.11.19.468202
Abstract: Agriculture must reduce green-house gas emission and pollution, produce safer and healthier food, closer to home, reducing waste whilst delivering more erse diets to a growing world population. Soils could enable this transformation, but unfortunately, they have a hugely complex and opaque structure and studies of its myriad of mechanisms are difficult. Here, the fabrication of smart soils for the screening of below-ground bio-processes is demonstrated. Particles were generated from fluoropolymer waste with functionalisation converting them into sensors able to report on key chemical dynamics. Tailored functionalization was obtained by radical terpolymerisation to improve growth conditions and sensing capabilities. The study demonstrates the potential for the development of accelerated genetic or agrochemical screens and could pave the way for improved models for rhizosphere dynamics.
Publisher: American Chemical Society (ACS)
Date: 19-03-2014
DOI: 10.1021/MZ5001527
Abstract: This study describes a facile and high yielding route to two series of polymethacrylates inspired by the naturally occurring, tryptophan-rich cationic antimicrobial polymers. Appropriate optimization of indole content within each gave rise to polymers with high potency against
Publisher: American Chemical Society (ACS)
Date: 27-06-2013
DOI: 10.1021/JM4006548
Abstract: Series of compounds were generated via the bioisosteric replacement of the carboxylate of 4-ACPCA (2) with hydroxamate or amide groups. All compounds from this study exhibited increased selectivity for GABAC, the most potent being 4-ACPHA (10a, IC50 = 13 μM) and 4-ACPAM (11a, IC50 = 10 μM). This provides evidence that a zwitterionic structure is not essential for GABAC antagonists, rather the emphasis lies in appropriate heteroatoms to participate in hydrogen bonding.
Publisher: American Chemical Society (ACS)
Date: 07-02-2012
DOI: 10.1021/CN200121R
Publisher: Elsevier
Date: 2016
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/CH16047
Abstract: Naturally occurring antimicrobial peptides have been honed by evolution over millions of years to give highly safe and efficacious antimicrobials that form part of many organisms’ immune systems. By studying these peptides to identify key aspects of structure and composition, suitable synthetic polymer mimics can be designed that hold potential as anti-infective agents. This review focusses on an important aspect of peptide mimicry, that of replicating the chemical functionality provided by key amino acids present in antimicrobial peptides. These include polymethacrylate mimics of arginine-rich and tryptophan-rich peptides. Systematic investigation of the structure–activity relationships of these polymers identifies the guanidine based poly(methylmethacrylate-co-2-guanidinoethyl methacrylate) (pMMA-co-GEMA) copolymers with low molecular weight and low methyl content as having superior activity profiles when compared with all other combinations. Unique antibiofilm activity of these polymers is also revealed in in vitro testing against monomicrobial and polymicrobial biofilms of the bacteria Staphylococcus aureus and the fungus Candida albicans. This highlights Mother Nature as an important resource in drug development and identifies the arginine-mimicking polymethacrylates as important leads for the development of a new generation of antimicrobial agents to tackle resistance.
Publisher: CSIRO
Date: 2019
Publisher: American Chemical Society (ACS)
Date: 10-06-2023
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D2MH00254J
Abstract: Non-biological complex drugs (NBCDs) are an emerging class of therapeutics that show multi-mechanistic antimicrobial activity and hold great promise as next generation antimicrobial agents.
Publisher: Frontiers Media SA
Date: 07-11-2019
Publisher: Elsevier BV
Date: 05-2020
Publisher: Oxford University Press (OUP)
Date: 21-10-2016
DOI: 10.1093/JAC/DKV334
Abstract: Biofilm-related human infections have high mortality rates due to drug resistance. Cohabitation of erse microbes in polymicrobial biofilms is common and these infections present additional challenges for treatment compared with monomicrobial biofilms. Here, we address this therapeutic gap by assessing the potential of a new class of antimicrobial agents, guanylated polymethacrylates, in the treatment of polymicrobial biofilms built by two prominent human pathogens, the fungus Candida albicans and the bacterium Staphylococcus aureus. We used imaging and quantitative methods to test the antibiofilm efficacy of guanylated polymethacrylates, a new class of drugs that structurally mimic antimicrobial peptides. We further compared guanylated polymethacrylates with first-line antistaphylococcal and anti-Candida agents used as combinatorial therapy against polymicrobial biofilms. Guanylated polymethacrylates were highly effective as a sole agent, killing both C. albicans and S. aureus when applied to established polymicrobial biofilms. Furthermore, they outperformed multiple combinations of current antimicrobial drugs, with one of the tested compounds killing 99.98% of S. aureus and 82.2% of C. albicans at a concentration of 128 mg/L. The extracellular biofilm matrix provided protection, increasing the MIC of the polymethacrylates by 2-4-fold when added to planktonic assays. Using the C. albicans bgl2ΔΔ mutant, we implicate matrix polysaccharide β-1,3 glucan in the mechanism of protection. Data for two structurally distinct polymers suggest that this mechanism could be minimized through chemical optimization of the polymer structure. Finally, we demonstrate that a potential application for these polymers is in antimicrobial lock therapy. Guanylated polymethacrylates are a promising lead for the development of an effective monotherapy against C. albicans/S. aureus polymicrobial biofilms.
Publisher: Walter de Gruyter GmbH
Date: 20-08-2014
Abstract: Host-defense antimicrobial peptides (AMPs) are a promising lead in the search for novel antibiotics. Many of these peptides exhibit broad-spectrum antibacterial ability, low toxicity toward human cells, and little susceptibility to induction of bacterial resistance. Our research focuses on the development of synthetic polymers that are able to mimic the hiphilic and cation-rich characteristics of AMPs. This derives bioactive polymers that retain the activity profile of AMPs while utilizing a construct that is less expensive and easier to produce and manipulate chemically. This review details structure–activity relationships (SARs) of a new class of arginine-rich, synthetic AMP mimicking polymers (SAMPs), the guanylated polymethacrylates. These are contrasted with those of amine-based polymers that are mimics of lysine-rich AMPs. The ideal composition for candidates for practical applications was identified as those containing guanidines as a cation source, having a low molecular weight and a low level of lipophilicity. This gave polymers with high potency against Gram-positive strains of bacteria (e.g., Staphylococcus epidermidis MIC = 10 μg/mL) and low toxicity towards human red blood cells ( % hemolysis at given MIC). This work emphasizes the need to rationalize observed biological activities based not purely on the global lipophilic and cationic character of polymers but rather to consider the profound effect that specific pendant functional groups may have on the potency, selectivity, and mechanisms behind the action of antimicrobial polymers.
Location: Australia
Location: Australia
No related grants have been discovered for Katherine Locock.