Biology subjects

Jolley, K. A.

Publications and source records attributed to Jolley, K. A..

25 records · Page 2Linked to original sources

bioRxiv2021

Inferring Mycobacterium bovis transmission between cattle and badgers using isolates from the Randomised Badger Culling Trial

Mycobacterium bovis (M. bovis) is a causative agent of bovine tuberculosis, a significant source of morbidity and mortality in the global cattle industry. The Randomised Badger Culling Trial was a field experiment carried out between 1998 and 2005 in the South West of England. As part of this trial, M. bovis isolates were collected from contemporaneous and overlapping populations of badgers and cattle within ten defined trial areas. We combined whole genome sequences from 1,442 isolates with location and cattle movement data, identifying transmission clusters and inferred rates and routes of transmission of M. bovis. Most trial areas contained a single transmission cluster that had been established shortly before sampling, often contemporaneous with the expansion of bovine tuberculosis in the 1980s. The estimated rate of transmission from badger to cattle was approximately two times higher than from cattle to badger, and the rate of within-species transmission considerably exceeded these for both species. We identified long distance transmission events linked to cattle movement, recurrence of herd breakdown by infection within the same transmission clusters and superspreader events driven by cattle but not badgers. Overall, our data suggests that the transmission clusters in different parts of South West England that are still evident today were established by long-distance seeding events involving cattle movement, not by recrudescence from a long-established wildlife reservoir. Clusters are maintained primarily by within-species transmission, with less frequent spill-over both from badger to cattle and cattle to badger.

genomics↗

bioRxiv2021

Establishment of a publicly available core genome multilocus sequence typing scheme for Clostridium perfringens

Clostridium perfringens is a spore-forming anaerobic pathogen responsible for a variety of histotoxic and intestinal infections in humans and animals. High-resolution genotyping aiming to identify bacteria at strain level has become increasingly important in modern microbiology to understand pathogen transmission pathways and to tackle infection sources. This study aimed at establishing a publicly available genome-wide multilocus sequence-typing scheme for C. perfringens. 1,431 highly conserved core genes (1.34 megabases; 50% of the reference genome genes) were indexed for a core-genome-based MLST scheme for C. perfringens. As an example, we applied the scheme to 87 poultry and 73 non-poultry strains (total=160). The genotyping results of the 160 genomes were congruent in terms of resolution and tree topology between allele-based and single-nucleotide-polymorphism-based core-genome typing. For the analysis of poultry strains of C. perfringens concerning the country of isolation, NetB-toxin gene carriage and clinical disease, we used 60 allelic differences as a clustering threshold. The results showed that poultry strains from a single country formed a cluster (n=17 clusters including 46 strains). Two clusters included six strains from four different countries. These strains were netB-positive, as were seven strains from Denmark and two strains from Finland, possibly indicating common sources of netB-positive strains. In terms of clinical presentation, different clusters of strains were associated with cases of suspected necrotic enteritis. Strains from sick birds grouped with strains from healthy birds or meat samples showing that potentially virulent strains are widespread and that host-related factors contribute significantly to NE. In summary, a publicly available scheme and an allele nomenclature database for genomic typing of C. perfringens has been established and can be used for broad-based and standardised epidemiological studies.

microbiology↗

bioRxiv2021

Cross-species evolutionary rewiring in the enteric bacterium Campylobacter

Significance StatementGenetic exchange among bacteria shapes the microbial world. From the acquisition of antimicrobial resistance genes to fundamental questions about the nature of bacterial species, this powerful evolutionary force has preoccupied scientists for decades. However, the mixing of genes between species rests on a paradox. On one hand, promoting adaptation by conferring novel functionality, on the other potentially introducing disharmonious gene combinations (negative epistasis) that will be selected against. Taking an interdisciplinary approach to analyse natural populations of the enteric bacteria Campylobacter, an ideal example of long-range admixture, we demonstrate that genes can independently transfer across species boundaries and rejoin in epistasis in a recipient genome. This challenges conventional ideas and highlights the possibility of single step evolution by saltation. AbstractRecombination of short DNA fragments via horizontal gene transfer (HGT) can both introduce beneficial alleles and create genomic disharmony through negative epistasis. For non-core (accessory) genes, the negative epistatic cost is likely to be minimal because the incoming genes have not co-evolved with the recipient genome. By contrast, for the core genome, interspecific recombination is expected to be rare because disruptive allelic replacement is likely to introduce negative epistasis. Why then is homologous recombination common in the core of bacterial genomes? To understand this enigma we take advantage of an exceptional model system, the common enteric pathogens Campylobacter jejuni and Campylobacter coli, that are known for very high magnitude interspecies gene flow in the core genome. As expected, HGT does indeed disrupt co-adapted allele pairings (negative epistasis). However, multiple HGT events enable recovery of the genomes co-adaption between introgressing alleles, even in core metabolism genes (e.g., formate dehydrogenase). These findings demonstrate that, even for complex traits, genetic coalitions can be decoupled, transferred and independently reinstated in a new genetic background - facilitating transition between fitness peaks. In this example, the two-step recombinational process is associated with C. coli that are adapted to the agricultural niche.

microbiology↗

bioRxiv2020

Evolution of ST-4821 clonal complex hyperinvasive and quinolone-resistant meningococci: the next meningococcal pandemic?

The expansion of quinolone-resistant Neisseria meningitidis clone ChinaCC4821-R1-C/B from ST-4821 clonal complex (cc4821) caused a serogroup shift from serogroup A to C in invasive meningococcal disease (IMD) in China. To establish the relationship among globally distributed cc4821 meningococci, we analysed whole genome sequence data from 173 cc4821 meningococci isolated in four continents from 1972-2019. These meningococci clustered into four sub-lineages (1-4), with sub-lineage 1 primarily comprising serogroup C IMD isolates (82%, 41/50). Most isolates from outside China formed a distinct sub-lineage (81.6%, 40/49, the Europe-USA cluster), with the typical strain designation B:P1.17-6,23:F3-36:ST-3200(cc4821) and harbouring mutations in penicillin-binding protein 2. These data show that the quinolone-resistant clone ChinaCC4821-R1-C/B has expanded to other countries. The increasing global distribution of B:cc4821 meningococci raises concern that cc4821 has the potential to cause a global pandemic and, this would be challenging to control though there is indirect evidence that Trumenba(R) vaccine might afford some protection.

bioinformatics↗

bioRxiv2020

Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index: a Rapid and Accessible Tool that Exploits Genomic Data in Public Health and Clinical Microbiology Applications

As microbial genomics makes increasingly important contributions to clinical and public health microbiology, the interpretation of whole genome sequence data by non-specialists becomes essential. In the absence of capsule-based vaccines, two protein-based vaccines have been used for the prevention of invasive serogroup B meningococcal disease (IMD), since their licensure in 2013/14. These vaccines have different components and different coverage of meningococcal variants. Hence, decisions regarding which vaccine to use in managing serogroup B IMD outbreaks require information about the index case isolate including: (i) the presence of particular vaccine antigen variants; (ii) the expression of vaccine antigens; and (iii) the likely susceptibility of its antigen variants to antibody-dependent bactericidal killing. To obtain this information requires a multitude of laboratory assays, impractical in real-time clinical settings, where the information is most urgently needed. To facilitate assessment for public health and clinical purposes, we synthesised genomic and experimental data from published sources to develop and implement the Meningococcal Deduced Vaccine Antigen Reactivity (MenDeVAR) Index, which is publicly-available on PubMLST (https://pubmlst.org). Using whole genome sequences or individual gene sequences obtained from IMD isolates or clinical specimens, MenDeVAR provides rapid evidence-based information on the presence and possible immunological cross-reactivity of different meningococcal vaccine antigen variants. The MenDeVAR Index enables practitioners who are not genomics specialists to assess the likely reactivity of vaccines for individual cases, outbreak management, or the assessment of public health vaccine programmes. MenDeVAR has been developed in consultation with, but independently of, both vaccine manufacturers.

genomics↗

bioRxiv2019

Domestication of Campylobacter jejuni NCTC 11168

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. Campylobacter 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 Campylobacter 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{degrees}C, invasion of chicken and human cell lines and susceptibility to ampicillin. 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.\n\nImpact statementIn 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 Campylobacter genomes and compare them with observable differences in common laboratory phenotypes.\n\nData summaryShort read data are archived on the NCBI SRA associated with BioProject accession PRJNA517467 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA517467).\n\nAll assembled genomes are also available on FigShare (doi: 10.6084/m9.figshare.7849268). Phylogeny visualised on microreact: https://microreact.org/project/NCTC11168.\n\nRepositoriesShort read data are archived on the NCBI SRA repository, associated with BioProject accession PRJNA517467 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA517467; Table S1).\n\nThe authors confirm all supporting data, code and protocols have been provided within the article or through supplementary data files.

microbiology↗

bioRxiv2017

Heterogeneity Among Estimates Of The Core Genome And Pan-Genome In Different Pneumococcal Populations

BackgroundUnderstanding the structure of a bacterial population is essential in order to understand bacterial evolution, or which genetic lineages cause disease, or the consequences of perturbations to the bacterial population. Estimating the core genome, the genes common to all or nearly all strains of a species, is an essential component of such analyses. The size and composition of the core genome varies by dataset, but our hypothesis was that variation between different collections of the same bacterial species should be minimal. To test this, the genome sequences of 3,121 pneumococci recovered from healthy individuals in Reykjavik (Iceland), Southampton (United Kingdom), Boston (USA) and Maela (Thailand) were analysed.\n\nResultsThe analyses revealed a supercore genome (genes shared by all 3,121 pneumococci) of only 303 genes, although 461 additional core genes were shared by pneumococci from Reykjavik, Southampton and Boston. Overall, the size and composition of the core genomes and pan-genomes among pneumococci recovered in Reykjavik, Southampton and Boston were very similar, but pneumococci from Maela were distinctly different. Inspection of the pan-genome of Maela pneumococci revealed several >25 Kb sequence regions that were homologous to genomic regions found in other bacterial species.\n\nConclusionsSome subsets of the global pneumococcal population are highly heterogeneous and thus our hypothesis was rejected. This is an essential point of consideration before generalising the findings from a single dataset to the wider pneumococcal population.

genomics↗