ORCID Profile
0000-0002-0751-0287
Current Organisation
University of Oxford
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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: 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: Public Library of Science (PLoS)
Date: 21-04-2016
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: 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: Cold Spring Harbor Laboratory
Date: 15-02-2023
DOI: 10.1101/2023.02.12.23285726
Abstract: Respiratory syncytial virus (RSV) is the leading cause of hospitalisation associated with acute respiratory infection in infants and young children, with substantial disease burden globally. The impact of additional respiratory pathogens on RSV disease severity is not completely understood. The objective of this study was to explore the associations between RSV disease severity and the presence of other respiratory pathogens. Nasopharyngeal swabs were prospectively collected from two infant cohorts: a prospective longitudinal birth cohort study and an infant cross-sectional study recruiting infants year of age with RSV infection in Spain, the UK, and the Netherlands during 2017–20 [part of the REspiratory Syncytial virus Consortium in EUrope (RESCEU) project]. The s les were sequenced using targeted metagenomic sequencing with a probe set optimised for high-resolution capture of sequences of over 100 pathogens, including all common respiratory viruses and bacteria. Viral genomes and bacterial genetic sequences were reconstructed. Associations between clinical severity and presence of other pathogens were evaluated after adjusting for potential confounders, including age, gestational age, RSV viral load, and presence of comorbidities. RSV was detected in 433 infants. Nearly one in four of the infants (24%) harboured at least one additional non-RSV respiratory virus, with human rhinovirus being the most frequently detected (15% of the infants), followed by seasonal coronaviruses (4%). In this cohort, RSV-infected infants harbouring any other virus tended to be older (median age: 4.3 vs. 3.7 months) and were more likely to require intensive care and mechanical ventilation than those who did not. Moraxella, Streptococcus , and Haemophilus species were the most frequently identified target bacteria, together found in 392 (91%) of the 433 infants ( S. pneumoniae in 51% of the infants and H. influenzae in 38%). The strongest contributors to severity of presentation were younger age and the co-detection of Haemophilus species alongside RSV. Across all age groups in both cohorts, detection of Haemophilus species was associated with higher overall severity, as captured by ReSVinet scores, and specifically with increased rates of hospitalisation and respiratory distress. In contrast, presence of Moraxella species was associated with lower ReSVinet scores and reduced need for intensive care and mechanical ventilation. Infants with and without Streptococcus species (or S. pneumoniae in particular) had similar clinical outcomes. No specific RSV strain was associated with co-detection of other pathogens. Our findings provide strong evidence for associations between RSV disease severity and the presence of additional respiratory viruses and bacteria. The associations, while not indicating causation, are of potential clinical relevance. Awareness of coexisting microorganisms could inform therapeutic and preventive measures to improve the management and outcome of RSV-infected infants.
Publisher: Public Library of Science (PLoS)
Date: 10-08-2020
Publisher: Oxford University Press (OUP)
Date: 29-11-2012
Publisher: Oxford University Press (OUP)
Date: 10-2011
Publisher: Public Library of Science (PLoS)
Date: 27-03-2014
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 08-2017
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: American Society for Microbiology
Date: 03-2010
DOI: 10.1128/JCM.01796-09
Abstract: A robust high-throughput multilocus sequence typing (MLST) scheme for Clostridium difficile was developed and validated using a erse collection of 50 reference isolates representing 45 different PCR ribotypes and 102 isolates from recent clinical s les. A total of 49 PCR ribotypes were represented overall. All isolates were typed by MLST and yielded 40 sequence types (STs). A web-accessible database was set up ( difficile/ ) to facilitate the dissemination and comparison of C. difficile MLST genotyping data among laboratories. MLST and PCR ribotyping were similar in discriminatory abilities, having indices of discrimination of 0.90 and 0.92, respectively. Some STs corresponded to a single PCR ribotype (32/40), other STs corresponded to multiple PCR ribotypes (8/40), and, conversely, the PCR ribotype was not always predictive of the ST. The total number of variable nucleotide sites in the concatenated MLST sequences was 103/3,501 (2.9%). Concatenated MLST sequences were used to construct a neighbor-joining tree which identified four phylogenetic groups of STs and one outlier (ST-11 PCR ribotype 078). These groups apparently correlate with clades identified previously by comparative genomics. The MLST scheme was sufficiently robust to allow direct genotyping of C. difficile in total stool DNA extracts without isolate culture. The direct (nonculture) MLST approach may prove useful as a rapid genotyping method, potentially benefiting in idual patients and informing hospital infection control.
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: Oxford University Press (OUP)
Date: 04-2017
DOI: 10.1093/GBE/EVX037
Publisher: Public Library of Science (PLoS)
Date: 19-05-2011
Publisher: Wiley
Date: 06-06-2006
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: Springer Science and Business Media LLC
Date: 22-03-2021
DOI: 10.1038/S41467-021-22238-5
Abstract: A Correction to this paper has been published: 0.1038/s41467-021-22238-5
Publisher: Wiley
Date: 25-04-2014
DOI: 10.1111/MEC.12742
Publisher: Wiley
Date: 04-2018
DOI: 10.1111/MEC.14546
Publisher: Springer Science and Business Media LLC
Date: 03-02-2021
DOI: 10.1038/S41467-021-20988-W
Abstract: Chickens are the most common birds on Earth and colibacillosis is among the most common diseases affecting them. This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic Escherichia coli (APEC), emerges from ubiquitous commensal gut bacteria, with no single virulence gene present in all disease-causing isolates. Here, we address the underlying evolutionary mechanisms of extraintestinal spread and systemic infection in poultry. Combining population scale comparative genomics and pangenome-wide association studies, we compare E. coli from commensal carriage and systemic infections. We identify phylogroup-specific and species-wide genetic elements that are enriched in APEC, including pathogenicity-associated variation in 143 genes that have erse functions, including genes involved in metabolism, lipopolysaccharide synthesis, heat shock response, antimicrobial resistance and toxicity. We find that horizontal gene transfer spreads pathogenicity elements, allowing ergent clones to cause infection. Finally, a Random Forest model prediction of disease status (carriage vs. disease) identifies pathogenic strains in the emergent ST-117 poultry-associated lineage with 73% accuracy, demonstrating the potential for early identification of emergent APEC in healthy flocks.
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: Cold Spring Harbor Laboratory
Date: 05-2020
DOI: 10.1101/2020.04.26.20075689
Abstract: C ylobacter is the leading bacterial cause of gastroenteritis worldwide and its incidence is especially high in low- and middle-income countries (LMIC). Disease epidemiology in LMICs is different compared to high income countries like the USA or in Europe. Children in LMICs commonly have repeated and chronic infections even in the absence of symptoms, which can lead to deficits in early childhood development. In this study, we sequenced and characterized C. jejuni (n=62) from a longitudinal cohort study of children under the age of 5 with and without diarrheal symptoms, and contextualized them within a global C. jejuni genome collection. Epidemiological differences in disease presentation were reflected in the genomes, specifically by the absence of some of the most common global disease-causing lineages. As in many other countries, poultry-associated strains were a major source of human infection but almost half of local disease cases (15 of 31) were attributable to genotypes that are rare outside of Peru. Asymptomatic infection was not limited to a single (or few) human adapted lineages but resulted from phylogenetically ergent strains suggesting an important role for host factors in the cryptic epidemiology of c ylobacteriosis in LMICs. C ylobacter is the leading bacterial cause of gastroenteritis worldwide and despite high incidence in low- and middle-income countries (LMICs), where infection can be fatal, culture based isolation is rare and the genotypes responsible for disease have not broadly been identified. The epidemiology of disease is different to that in high income countries, where sporadic infection associated with contaminated food consumption typically leads to acute gastroenteritis. In some LMICs infection is endemic among children and common asymptomatic carriage is associated with malnutrition, attenuated growth in early childhood, and poor cognitive and physical development. Here, we sequenced the genomes of isolates s led from children in the Peruvian Amazon to investigate genotypes associated with varying disease severity and the source of infection. Among the common globally circulating genotypes and local genotypes rarely seen before, no single lineage was responsible for symptomatic or asymptomatic infection – suggesting an important role for host factors. However, consistent with other countries, poultry-associated strains were a major source of infection. This genomic surveillance approach, that integrates microbial ecology with population based studies in humans and animals, has considerable potential for describing cryptic epidemiology in LMICs and will inform work to improve infant health worldwide.
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
No related grants have been discovered for Keith Jolley.