ORCID Profile
0000-0001-6321-5138
Current Organisations
University of Oxford Hertford College
,
University of Oxford
,
The Royal College of Pathologists
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Publisher: Proceedings of the National Academy of Sciences
Date: 07-2013
Abstract: Genome-wide association studies have the potential to identify causal genetic factors underlying important phenotypes but have rarely been performed in bacteria. We present an association mapping method that takes into account the clonal population structure of bacteria and is applicable to both core and accessory genome variation. C ylobacter is a common cause of human gastroenteritis as a consequence of its proliferation in multiple farm animal species and its transmission via contaminated meat and poultry. We applied our association mapping method to identify the factors responsible for adaptation to cattle and chickens among 192 C ylobacter isolates from these and other host sources. Phylogenetic analysis implied frequent host switching but also showed that some lineages were strongly associated with particular hosts. A seven-gene region with a host association signal was found. Genes in this region were almost universally present in cattle but were frequently absent in isolates from chickens and wild birds. Three of the seven genes encoded vitamin B 5 biosynthesis. We found that isolates from cattle were better able to grow in vitamin B 5 -depleted media and propose that this difference may be an adaptation to host diet.
Publisher: Public Library of Science (PLoS)
Date: 15-03-2016
Publisher: Cambridge University Press (CUP)
Date: 08-1998
DOI: 10.1017/S0950268898008942
Abstract: Changes in the frequency of serogroup B non serotypable (B[ratio ]NT) meningococci isolated in England and Wales were investigated by T-track fingerprint analysis, DNA nucleotide sequence determination, and serotyping by whole cell ELISA and dot blot assay. Seventy-three per cent of the isolates designated as B[ratio ]NT by the Meningococcal Reference Unit (MRU) dot blot assay during 1993–4, expressed variants of the serotyping antigen, PorB, that were serotype 4 by whole cell ELISA. T-track fingerprint patterns of these and other ‘serotype 4’ isolates revealed five distinct porB alleles which were shown by nucleotide sequence determination to encode different peptide sequences. Differential binding of the ‘serotype 4’ mAbs MN14G21 and 5DC4C8G8 in whole cell ELISA and dot blot assays was the result, (i) of differences in the peptide sequence of predicted surface loop I and (ii) an amino acid deletion in predicted loop VI of the PorB protein.
Publisher: Microbiology Society
Date: 07-2019
Abstract: Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterized isolates among laboratories has run in parallel with research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. C ylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first C ylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C . jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates, identified previously to have aberrant phenotypes, varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37 °C, invasion of chicken and human cell lines, and susceptibility to icillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. This article contains data hosted by Microreact .
Publisher: eLife Sciences Publications, Ltd
Date: 03-02-2022
Publisher: Elsevier BV
Date: 10-2003
DOI: 10.1016/J.TIM.2003.08.006
Abstract: The characterization of pathogenic isolates plays a pivotal role in the epidemiology of infectious diseases, generating the information necessary for identifying, tracking, and intervening against disease outbreaks. In 1998 multi-locus sequence typing (MLST) was proposed as a nucleotide sequence-based approach that could be applied to many bacterial pathogens. It combined developments in high-throughput sequencing and bioinformatics with established population genetics techniques to provide a portable, reproducible, and scalable typing system that reflected the population and evolutionary biology of bacterial pathogens. MLST schemes have been developed for a variety of procaryotic and eucaryotic pathogens and the data generated have contributed to both epidemiological surveillance and fundamental studies of pathogen biology.
Publisher: American Society for Microbiology
Date: 02-2006
DOI: 10.1128/AEM.72.2.1420-1428.2006
Abstract: Intramammary infection with Streptococcus uberis is a common cause of bovine mastitis throughout the world. Several procedures to differentiate S. uberis isolates have been proposed. However, all are prone to interlaboratory variation, and none is suitable for the description of the population structure. We describe here the development of a multilocus sequence typing (MLST) scheme for S. uberis to help address these issues. The sequences of seven housekeeping gene fragments from each of 160 United Kingdom milk isolates of S. uberis were determined. Between 5 and 17 alleles were obtained per locus, giving the potential to discriminate between 1.3 × 10 7 sequence types. In this study, 57 sequence types (STs) were identified. Statistical comparisons between the maximum-likelihood trees constructed by using the seven housekeeping gene fragments showed that the congruence was no better than that between each tree and trees of random topology, indicating there had been significant recombination within these loci. The population contained one major lineage (designated the ST-5 complex). This dominated the population, containing 24 STs and representing 112 isolates. The other 33 STs were not assigned to any clonal complex. All of the isolates in the ST-5 lineage carried hasA , a gene that is essential for capsule production. There was no clear association between ST or clonal complex and disease. The S. uberis MLST system offers researchers a valuable tool that allows further investigation of the population biology of this organism and insights into the epidemiology of this disease on a global scale.
Publisher: Microbiology Society
Date: 10-2009
Abstract: Despite the increasing popularity of multilocus sequence typing (MLST), the most appropriate method for characterizing bacterial variation and facilitating epidemiological investigations remains a matter of debate. Here, we propose that different typing schemes should be compared on the basis of their power to infer clonal relationships and investigate the utility of sequence data for genealogical reconstruction by exploiting new statistical tools and data from 20 housekeeping loci for 93 isolates of the bacterial pathogen Neisseria meningitidis . Our analysis demonstrated that all but one of the hyperinvasive isolates established by multilocus enzyme electrophoresis and MLST were grouped into one of six genealogical lineages, each of which contained substantial variation. Due to the confounding effect of recombination, evolutionary relationships among these lineages remained unclear, even using 20 loci. Analyses of the seven loci in the standard MLST scheme using the same methods reproduced this classification, but were unable to support finer inferences concerning the relationships between the members within each complex.
Publisher: Cold Spring Harbor Laboratory
Date: 18-04-2019
DOI: 10.1101/591701
Abstract: Reference and type strains of well-known bacteria have been a cornerstone of microbiology research for decades. The sharing of well-characterised isolates among laboratories has parallelised research efforts and enhanced the reproducibility of experiments, leading to a wealth of knowledge about trait variation in different species and the underlying genetics. C ylobacter jejuni strain NCTC 11168, deposited at the National Collection of Type Cultures in 1977, has been adopted widely as a reference strain by researchers worldwide and was the first C ylobacter for which the complete genome was published (in 2000). In this study, we collected 23 C. jejuni NCTC 11168 reference isolates from laboratories across the UK and compared variation in simple laboratory phenotypes with genetic variation in sequenced genomes. Putatively identical isolates identified previously to have aberrant phenotypes varied by up to 281 SNPs (in 15 genes) compared to the most recent reference strain. Isolates also display considerable phenotype variation in motility, morphology, growth at 37°C, invasion of chicken and human cell lines and susceptibility to icillin. This study provides evidence of ongoing evolutionary change among C. jejuni isolates as they are cultured in different laboratories and highlights the need for careful consideration of genetic variation within laboratory reference strains. In this paper, we comment on the changing role of laboratory reference strains. While the model organism allows basic comparison within and among laboratories, it is important to remember the effect even small differences in isolate genomes can have on the validity and reproducibility of experimental work. We quantify differences in 23 reference C ylobacter genomes and compare them with observable differences in common laboratory phenotypes. Short read data are archived on the NCBI SRA associated with BioProject accession PRJNA517467 ( ioproject/PRJNA517467 ). All assembled genomes are also available on FigShare (doi: 10.6084/m9.figshare.7849268). Phylogeny visualised on microreact: roject/NCTC11168 . Short read data are archived on the NCBI SRA repository, associated with BioProject accession PRJNA517467 ( ioproject/PRJNA517467 Table S1 ). The authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.
Publisher: Oxford University Press (OUP)
Date: 10-2002
DOI: 10.1093/OXFORDJOURNALS.MOLBEV.A003991
Abstract: Previous estimates of rates of synonymous (d(S)) and nonsynonymous (d(N)) substitution among Neisseria meningitidis gene sequences suggested that the surface loops of the variable outer membrane protein PorB were under only weak selection pressure from the host immune response. These findings were consistent with studies indicating that PorB variants were not always protective in immunological and microbiological assays and questioned the suitability of this protein as a vaccine component. PorB, which is expressed at high levels on the surface of the meningococcus, has been implicated in mechanisms of pathogenesis and has also been used as a typing target in epidemiological investigations. In this work, using more precise estimates of selection pressures and recombination rates, we have shown that some residues in the surface loops of PorB are under very strong positive selection, as great as that observed in human immunodeficiency virus-1 surface glycoproteins, whereas amino acids within the loops and the membrane-spanning regions of the protein are under purifying selection, presumably because of structural constraints. Congruence tests showed that recombination occurred at a rate that was not sufficient to erase all phylogenetic similarity and did not greatly bias selection analysis. Homology models of PorB structure indicated that many strongly selected sites encoded residues that were predicted to be exposed to host immune responses, implying that this protein is under strong immune selection and requires further examination as a potential vaccine candidate. These data show that phylogenetic inference can be used to complement immunological and biochemical data in the choice of vaccine candidates.
Publisher: Oxford University Press (OUP)
Date: 06-04-2015
DOI: 10.1093/NAR/GKV219
Publisher: Oxford University Press (OUP)
Date: 06-1999
DOI: 10.1093/OXFORDJOURNALS.MOLBEV.A026159
Abstract: The extent to which recombination disrupts the bifurcating treelike phylogeny and clonal structure imposed by binary fission on bacterial populations remains contentious. Here, we address this question with a study of nucleotide sequence data from 107 isolates of the human pathogen Neisseria meningitidis. Gene fragments from 12 house-keeping loci distributed around the meningococcal chromosome were analyzed, showing that (1) identical alleles are disseminated among genetically erse isolates, with no evidence for linkage disequilibrium (2) different loci give distinct and incongruent phylogenetic trees and (3) allele sequences are incompatible with a bifurcating treelike phylogeny at all loci. These observations are consistent with the hypothesis that meningococcal populations comprise organisms assembled from a common gene pool, with alleles and allele fragments spreading independently, together with the occasional importation of genetic material from other species. Further, they support the view that recombination is an important genetic mechanism in the generation new meningococcal clones and alleles. Consequently, for anything other than the short-term evolution of this species, a bifurcating treelike phylogeny is not an appropriate model.
Publisher: Massachusetts Medical Society
Date: 23-01-2020
Publisher: Oxford University Press (OUP)
Date: 10-2011
Publisher: Public Library of Science (PLoS)
Date: 27-03-2014
Publisher: Microbiology Society
Date: 08-2011
Abstract: Invasive disease caused by the encapsulated bacteria Neisseria meningitidis , Haemophilus influenzae and Streptococcus pneumoniae remains an important cause of morbidity and mortality worldwide, despite the introduction of successful conjugate polysaccharide vaccines that target disease-associated strains. In addition, resistance, or more accurately reduced susceptibility, to therapeutic antibiotics is spreading in populations of these organisms. There is therefore a continuing requirement for the surveillance of vaccine and non-vaccine antigens and antibiotic susceptibilities among isolates from invasive disease, which is only partially met by conventional methods. This need can be met with molecular and especially nucleotide sequence-based typing methods, which are fully developed in the case of N. meningitidis and which could be more widely deployed in clinical laboratories for S. pneumoniae and H. influenzae .
Publisher: Microbiology Society
Date: 04-2008
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JINF.2014.07.002
Abstract: To assess the potential use of a protein-based meningococcal group B (MenB) vaccine (Bexsero(®)) in addition to antibiotic chemoprophylaxis for preventing secondary cases. Published studies on the risk of secondary meningococcal infections were used to estimate the numbers needed to vaccinate (NNV) with Bexsero(®) to prevent a secondary case in household and educational settings. Most secondary cases occur within a few days of diagnosis in the index case. Unlike conjugate vaccines, early protection offered after a single dose of Bexsero(®) is likely to be low, particularly in young children, who are at higher risk of secondary infection. NNV was dependent on predicted meningococcal strain coverage, estimated onset of protection after one Bexsero(®) dose and estimated vaccine efficacy. Even in the most favourable scenario where we assume the vaccine is administered within 4 days of the index case and prevents 90% of cases occurring after 14 days, the NNV for household contacts was >1000. NNV in educational settings was much higher. The estimated NNV should be taken into account when deciding policy to recommend Bexsero(®) for close contacts of single cases in household or educational settings. Bexsero(®) may have a protective role in clusters and outbreaks.
Publisher: Microbiology Society
Date: 05-2002
Publisher: Oxford University Press (OUP)
Date: 03-2008
DOI: 10.1086/527401
Abstract: Background. In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. Methods. Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 s les, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. Results. A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06) these meningococci also exhibited high rates of capsule expression. Conclusions. The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.
Publisher: American Society for Microbiology
Date: 03-2010
DOI: 10.1128/JCM.01653-09
Abstract: In response to epidemic levels of serogroup B meningococcal disease in Cuba during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the National Infant Immunization Program in 1991. Since then the incidence of meningococcal disease in Cuba has returned to the low levels recorded before the epidemic. A total of 420 Neisseria meningitidis strains collected between 1983 and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of strains comprised 167 isolated from disease cases and 253 obtained from healthy carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of these were reported to be a new ST. The Cuban isolates were associated with 12 clonal complexes and the most common were ST-32 (246 isolates), ST-53 (86 isolates), and ST-41/44 (36 isolates). This study also showed that the application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the frequency and ersity of hypervirulent clonal complexes ST-32 (vaccine serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages ST-8 and ST-11 were no longer found during the postvaccination period. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST.
Publisher: Springer Science and Business Media LLC
Date: 12-02-2016
DOI: 10.1038/SREP21015
Abstract: Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease however, those belonging to the ‘hyperinvasive lineages’ are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase vari able regul ons (phasevarions), have been identified in N. meningitidis . Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and ,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11 - 12 and modB1-2 were found in most isolates, rarer alleles ( e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains.
Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2021
DOI: 10.1101/2021.08.24.457495
Abstract: Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus C ylobacter there are species with ergent ecologies, from rarely isolated single host specialists to multi-host generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterising these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analysing recipient and donor population ancestry among genomes from 30 C ylobacter species we show that cohabitation in the same host can lead to a 6-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.
Publisher: American Society for Microbiology
Date: 02-2013
DOI: 10.1128/AEM.02521-12
Abstract: Closely related bacterial isolates can display ergent phenotypes. This can limit the usefulness of phylogenetic studies for understanding bacterial ecology and evolution. Here, we compare phenotyping based on Raman spectrometric analysis of cellular composition to phylogenetic classification by ribosomal multilocus sequence typing (rMLST) in 108 isolates of the zoonotic pathogens C ylobacter jejuni and C. coli . Automatic relevance determination (ARD) was used to identify informative peaks in the Raman spectra that could be used to distinguish strains in taxonomic and host source groups (species, clade, clonal complex, and isolate source/host). Phenotypic characterization based on Raman spectra showed a degree of agreement with genotypic classification using rMLST, with segregation accuracy between species (83.95%), clade (in C. coli , 98.41%), and, to some extent, clonal complex (86.89% C. jejuni ST-21 and ST-45 complexes) being achieved. This confirmed the utility of Raman spectroscopy for lineage classification and the correlation between genotypic and phenotypic classification. In parallel analysis, relatively distantly related isolates (different clonal complexes) were assigned the correct host origin irrespective of the clonal origin (74.07 to 96.97% accuracy) based upon different Raman peaks. This suggests that the phenotypic characteristics, from which the phenotypic signal is derived, are not fixed by clonal descent but are influenced by the host environment and change as strains move between hosts.
Publisher: American Society for Microbiology
Date: 10-2004
DOI: 10.1128/IAI.72.10.5955-5962.2004
Abstract: The bacterium Neisseria meningitidis is a major cause of meningitis and septicemia worldwide. Outer membrane proteins (OMPs) are candidates in the search for comprehensive meningococcal vaccines however, the formulation of OMP vaccines is complicated by antigenic ersity, which is generated by high levels of genetic reassortment and strong positive selection in the meningococcal antigen genes. The genetic and antigenic ersity of three OMPs (FetA, PorA, and PorB) among a global collection of meningococcal isolates representative of the major hyperinvasive clonal complexes was determined. There was evidence for antigenic structuring among the three OMPs that could not be explained purely by descent. These observations violated the predictions of the clonal and epidemic clonal models of population structure but were in concordance with models of strain structure which propose that host immunity selects for nonoverlapping antigen combinations. The patterns of antigenic variant combinations suggested that an OMP-based vaccine with as few as six PorA and five FetA variant sequences could generate homologous immune responses against all 78 isolates examined.
Publisher: Cambridge University Press (CUP)
Date: 06-1998
DOI: 10.1017/S0950268898008656
Abstract: Since 1992, the proportion of culture-confirmed meningococcal infections compared with numbers of notified cases of meningococcal disease has decreased in England and Wales. As most meningococcal strain characterization methods depend on a clinical isolate, this has resulted in a loss of epidemiological information. To address this problem, and to aid non-culture diagnosis, a semi-nested PCR protocol for the lification of the meningococcal porB gene from clinical specimens was developed. This gene encodes the meningococcal serotyping antigen strain typing data was provided by hybridization of allele-specific oligonucleotide probes to the digoxigenin-labelled porB licon in a ‘PCR ELISA’. This assay was specific for meningococcal DNA and sensitivities of 0·81 for cerebrospinal fluid (CSF), 0·57 for serum, and 0·62 for whole blood taken from patients with proven meningococcal infection were obtained.
Publisher: BMJ
Date: 10-2019
DOI: 10.1136/BMJOPEN-2020-037358
Abstract: Capsular group B Neisseria meningitidis (MenB) is the most common cause of invasive meningococcal disease (IMD) in many parts of the world. A MenB vaccine directed against the polysaccharide capsule remains elusive due to poor immunogenicity and safety concerns. The vaccines licensed for the prevention of MenB disease, 4CMenB (Bexsero) and MenB-fHbp (Trumenba), are serogroup B ‘substitute’ vaccines, comprised of subcapsular proteins and are designed to provide protection against most MenB disease-causing strains. In many high-income countries, such as the UK, adolescents are at increased risk of IMD and have the highest rates of meningococcal carriage. Beginning in the late 1990s, immunisation of this age group with the meningococcal group C conjugate vaccine reduced asymptomatic carriage and disrupted transmission of this organism, resulting in lower group C IMD incidence across all age groups. Whether vaccinating teenagers with the novel ‘MenB’ protein-based vaccines will prevent acquisition or reduce duration of carriage and generate herd protection was unknown at the time of vaccine introduction and could not be inferred from the effects of the conjugate vaccines. 4CMenB and MenB-fHbp may also impact on non-MenB disease-causing capsular groups as well as commensal Neisseria spp. This study will evaluate the impact of vaccination with 4CMenB or MenB-fHbp on oropharyngeal carriage of pathogenic meningococci in teenagers, and consequently the potential for these vaccines to provide broad community protection against MenB disease. The ‘Be on the TEAM’ (Teenagers Against Meningitis) Study is a pragmatic, partially randomised controlled trial of 24 000 students aged 16–19 years in their penultimate year of secondary school across the UK with regional allocation to a 0+6 month schedule of 4CMenB or MenB-fHbp or to a control group. Culture-confirmed oropharyngeal carriage will be assessed at baseline and at 12 months, following which the control group will be eligible for 4CMenB vaccination. The primary outcome is the carriage prevalence of potentially pathogenic meningococci (defined as those with genogroups B, C, W, Y or X), in each vaccine group compared separately to the control group at 12 months post-enrolment, that is, 12 months after the first vaccine dose and 6 months after the second vaccine dose. Secondary outcomes include impact on carriage of: genogroup B meningococci hyperinvasive meningococci all meningococci those meningococci expressing vaccine antigens and other Neisseria spp. A s le size of 8000 in each arm will provide 80% power to detect a 30% reduction in meningococcal carriage, assuming genogroup B, C, W, Y or X meningococci carriage of 3.43%, a design effect of 1.5, a retention rate of 80% and a significance level of 0.05. Study results will be available in 2021 and will inform the UK and international immunisation policy and future vaccine development. This study is approved by the National Health Service South Central Research Ethics Committee (18/SC/0055) the UK Health Research Authority (IRAS ID 239091) and the UK Medicines and Healthcare products Regulatory Agency. Publications arising from this study will be submitted to peer-reviewed journals. Study results will be disseminated in public forums, online, presented at local and international conferences and made available to the participating schools. ISRCTN75858406 Pre-results, EudraCT 2017-004609-42.
Publisher: Wiley
Date: 29-01-2013
DOI: 10.1111/MEC.12144
Publisher: Elsevier BV
Date: 09-2000
Publisher: American Society for Microbiology
Date: 04-2001
DOI: 10.1128/JCM.39.4.1235-1240.2001
Abstract: Characterization of isolates of Neisseria meningitidis obtained from patients with meningococcal disease or from pharyngeal swabs of asymptomatic carriers can be achieved by several approaches which provide different levels of discrimination. A total of 45 gram negative, oxidase-positive diplococcus strains isolated from 15 in iduals with meningococcal disease and 30 of their family contacts were examined by three approaches: serological typing, multilocus enzyme electrophoresis (MLEE), and multilocus sequence typing (MLST). For 10 of the 15 patient and contact groups, all of the isolates were confirmed as meningococci, and the bacteria obtained from the patients and contacts, including their mother or principal caregiver in the case of children, were indistinguishable by all three methods. In the remaining five groups the isolates from the patients were distinct from those recovered from the contacts, and in three ex les, in two separate groups, the contacts were shown by MLST to be carrying strains of Neisseria lactamica . The data obtained from the three techniques were consistent, although complete serological typing was possible for only a minority of isolates. Both MLEE and MLST established the genetic relationships of the isolates and identified members of known hypervirulent lineages, but MLST was faster than MLEE and had the additional advantages that it could be performed on noninfective material distributed by mail and that the results from different laboratories could be compared via the internet ( mlst.zoo.ox.ac.uk ).
Publisher: Springer Science and Business Media LLC
Date: 28-11-2018
DOI: 10.1038/S41467-018-07368-7
Abstract: Some of the most common infectious diseases are caused by bacteria that naturally colonise humans asymptomatically. Combating these opportunistic pathogens requires an understanding of the traits that differentiate infecting strains from harmless relatives. Staphylococcus epidermidis is carried asymptomatically on the skin and mucous membranes of virtually all humans but is a major cause of nosocomial infection associated with invasive procedures. Here we address the underlying evolutionary mechanisms of opportunistic pathogenicity by combining pangenome-wide association studies and laboratory microbiology to compare S. epidermidis from bloodstream and wound infections and asymptomatic carriage. We identify 61 genes containing infection-associated genetic elements (k-mers) that correlate with in vitro variation in known pathogenicity traits (biofilm formation, cell toxicity, interleukin-8 production, methicillin resistance). Horizontal gene transfer spreads these elements, allowing ergent clones to cause infection. Finally, Random Forest model prediction of disease status (carriage vs. infection) identifies pathogenicity elements in 415 S. epidermidis isolates with 80% accuracy, demonstrating the potential for identifying risk genotypes pre-operatively.
Publisher: Public Library of Science (PLoS)
Date: 24-04-2009
Publisher: Wiley
Date: 25-04-2014
DOI: 10.1111/MEC.12742
Publisher: Springer Science and Business Media LLC
Date: 06-2012
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.MEEGID.2010.02.002
Abstract: We investigated the population genetics in collections of meningococci s led in Cuba during the period 1983-2005, thereby covering a period before and after the introduction of an antimeningococcal B-C vaccine. A total of 163 case isolates and 210 isolates from healthy carriers were characterized by multilocus sequence typing (MLST) and sequence determination of porA, porB and fetA genes. A total of 56 sequence types (STs) including 28 new STs were identified among these isolates. The analysis of surface antigens revealed variants 3-1 and 3-8 to be prevalent for porB variant F5-1 was the most common FetA epitope, and variants 19 and 15 corresponded to the prevalent variable regions 1 (VR1) and VR2 PorA epitopes, respectively. The strongest associations between specific surface protein variants and clonal complexes were detected in lineages ST-32 and ST-53. All ST-32 complex isolates possessed porB3 alleles, and the most frequent antigen combination among ST-32 complex isolates was P1.19,15 F5-1. Variants PorB3-64 at PorB and P1.30 at PorA VR2, in combination with the PorA VR1 variants P1.12-1, P1.7 and P1.7-2 as well as the FetA variants F1-2 and F1-7, dominated the ST-53 complex organisms. Furthermore, we observed a statistically significant association between the most frequent porA, porB and fetA alleles and strain invasiveness. Finally, this study showed that the application of VA-MENGOC-BC((R)), the Cuban antimeningococcal vaccine, reduced the number and frequency of the hypervirulent Clonal Complexes ST-32 and ST-41/44, and also impacted on other lineages. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST.
Publisher: Oxford University Press (OUP)
Date: 15-04-2005
DOI: 10.1086/428590
Abstract: Neisseria meningitidis is a erse commensal bacterium that occasionally causes severe invasive disease. The relationship between meningococcal genotype and capsular polysaccharide, the principal virulence factor and vaccine component, was investigated in carried meningococci isolated from 8000 children and young adults in Bavaria, Germany. Of the 830 meningococci isolated (carriage rate, 10.4%) by microbiological techniques, 822 were characterized by serogrouping, multilocus sequence typing, and genetic analysis of the capsule region. Statistical and population genetic analyses were applied to these data. The rapid increase in carriage rates with age of carrier, the low prevalence of hyperinvasive meningococci, and the relative prevalence of the 4 disease-associated serogroups were consistent with earlier observations. There was no genetic structuring of the meningococcal population by age of carrier or s ling location however, there was significant geographic structuring of the meningococci isolated in civil, but not military, institutions. The rate of capsule gene expression did not vary with age of carrier or meningococcal genotype, except for serogroup C, for which increased expression was associated with ST-11 (formerly ET-37) complex meningococci. Serogroup C capsule expression during carriage may contribute to the invasive character of ST-11 complex meningococci and to the high efficacy of meningococcal serogroup C conjugate polysaccharide vaccine.
Publisher: Wiley
Date: 04-05-2006
Publisher: Proceedings of the National Academy of Sciences
Date: 17-03-1998
Abstract: Traditional and molecular typing schemes for the characterization of pathogenic microorganisms are poorly portable because they index variation that is difficult to compare among laboratories. To overcome these problems, we propose multilocus sequence typing (MLST), which exploits the unambiguous nature and electronic portability of nucleotide sequence data for the characterization of microorganisms. To evaluate MLST, we determined the sequences of ≈470-bp fragments from 11 housekeeping genes in a reference set of 107 isolates of Neisseria meningitidis from invasive disease and healthy carriers. For each locus, alleles were assigned arbitrary numbers and dendrograms were constructed from the pairwise differences in multilocus allelic profiles by cluster analysis. The strain associations obtained were consistent with clonal groupings previously determined by multilocus enzyme electrophoresis. A subset of six gene fragments was chosen that retained the resolution and congruence achieved by using all 11 loci. Most isolates from hyper-virulent lineages of serogroups A, B, and C meningococci were identical for all loci or differed from the majority type at only a single locus. MLST using six loci therefore reliably identified the major meningococcal lineages associated with invasive disease. MLST can be applied to almost all bacterial species and other haploid organisms, including those that are difficult to cultivate. The overwhelming advantage of MLST over other molecular typing methods is that sequence data are truly portable between laboratories, permitting one expanding global database per species to be placed on a World-Wide Web site, thus enabling exchange of molecular typing data for global epidemiology via the Internet.
Publisher: eLife Sciences Publications, Ltd
Date: 22-02-2022
DOI: 10.7554/ELIFE.73552
Abstract: Horizontal gene transfer (HGT) can allow traits that have evolved in one bacterial species to transfer to another. This has potential to rapidly promote new adaptive trajectories such as zoonotic transfer or antimicrobial resistance. However, for this to occur requires gaps to align in barriers to recombination within a given time frame. Chief among these barriers is the physical separation of species with distinct ecologies in separate niches. Within the genus C ylobacter, there are species with ergent ecologies, from rarely isolated single-host specialists to multihost generalist species that are among the most common global causes of human bacterial gastroenteritis. Here, by characterizing these contrasting ecologies, we can quantify HGT among sympatric and allopatric species in natural populations. Analyzing recipient and donor population ancestry among genomes from 30 C ylobacter species, we show that cohabitation in the same host can lead to a six-fold increase in HGT between species. This accounts for up to 30% of all SNPs within a given species and identifies highly recombinogenic genes with functions including host adaptation and antimicrobial resistance. As described in some animal and plant species, ecological factors are a major evolutionary force for speciation in bacteria and changes to the host landscape can promote partial convergence of distinct species through HGT.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
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