Publications
197 results found
Brown T, Didelot X, Wilson DJ, et al., 2016, SimBac: simulation of whole bacterial genomes with homologous recombination., Microbial Genomics, Vol: 2, ISSN: 2057-5858
Bacteria can exchange genetic material, or acquire genes found in the environment. This process, generally known as bacterial recombination, can have a strong impact on the evolution and phenotype of bacteria, for example causing the spread of antibiotic resistance across clades and species, but can also disrupt phylogenetic and transmission inferences. With the increasing affordability of whole genome sequencing, the need has emerged for an efficient simulator of bacterial evolution to test and compare methods for phylogenetic and population genetic inference, and for simulation-based estimation. We present SimBac, a whole-genome bacterial evolution simulator that is roughly two orders of magnitude faster than previous software and includes a more general model of bacterial evolution, allowing both within- and between-species homologous recombination. Since methods modeling bacterial recombination generally focus on only one of these two modes of recombination, the possibility to simulate both allows for a general and fair benchmarking. SimBac is available from http://github.com/tbrown91/SimBac and is distributed as open source under the terms of the GNU General Public License.
Yahara K, Didelot X, Jolley KA, et al., 2015, The Landscape of Realized Homologous Recombination in Pathogenic Bacteria, Molecular Biology and Evolution, Vol: 33, Pages: 456-471, ISSN: 1537-1719
Recombination enhances the adaptive potential of organisms by allowing genetic variants to be tested on multiple genomic backgrounds. Its distribution in the genome can provide insight into the evolutionary forces that underlie traits, such as the emergence of pathogenicity. Here, we examined landscapes of realized homologous recombination of 500 genomes from ten bacterial species and found all species have “hot” regions with elevated rates relative to the genome average. We examined the size, gene content, and chromosomal features associated with these regions and the correlations between closely related species. The recombination landscape is variable and evolves rapidly. For example in Salmonella, only short regions of around 1 kb in length are hot whereas in the closely related species Escherichia coli, some hot regions exceed 100 kb, spanning many genes. Only Streptococcus pyogenes shows evidence for the positive correlation between GC content and recombination that has been reported for several eukaryotes. Genes with function related to the cell surface/membrane are often found in recombination hot regions but E. coli is the only species where genes annotated as “virulence associated” are consistently hotter. There is also evidence that some genes with “housekeeping” functions tend to be overrepresented in cold regions. For example, ribosomal proteins showed low recombination in all of the species. Among specific genes, transferrin-binding proteins are recombination hot in all three of the species in which they were found, and are subject to interspecies recombination.
Joseph SJ, Marti H, Didelot X, et al., 2015, Chlamydiaceae Genomics Reveals Interspecies Admixture and the Recent Evolution of Chlamydia abortus Infecting Lower Mammalian Species and Humans, Genome Biology and Evolution, Vol: 7, Pages: 3070-3084, ISSN: 1759-6653
Chlamydiaceae are obligate intracellular bacteria that cause a diversity of severe infections among humans and livestock on a global scale. Identification of new species since 1989 and emergence of zoonotic infections, including abortion in women, underscore the need for genome sequencing of multiple strains of each species to advance our knowledge of evolutionary dynamics across Chlamydiaceae. Here, we genome sequenced isolates from avian, lower mammalian and human hosts. Based on core gene phylogeny, five isolates previously classified as Chlamydia abortus were identified as members of Chlamydia psittaci and Chlamydia pecorum. Chlamydia abortus is the most recently emerged species and is a highly monomorphic group that lacks the conserved virulence-associated plasmid. Low-level recombination and evidence for adaptation to the placenta echo evolutionary processes seen in recently emerged, highly virulent niche-restricted pathogens, such as Bacillus anthracis. In contrast, gene flow occurred within C. psittaci and other Chlamydiaceae species. The C. psittaci strain RTH, isolated from a red-tailed hawk (Buteo jamaicensis), is an outlying strain with admixture of C. abortus, C. psittaci, and its own population markers. An average nucleotide identity of less than 94% compared with other Chlamydiaceae species suggests that RTH belongs to a new species intermediary between C. psittaci and C. abortus. Hawks, as scavengers and predators, have extensive opportunities to acquire multiple species in their intestinal tract. This could facilitate transformation and homologous recombination with the potential for new species emergence. Our findings indicate that incubator hosts such as birds-of-prey likely promote Chlamydiaceae evolution resulting in novel pathogenic lineages.
Achtman M, Zhou Z, Didelot X, 2015, Formal Comment to Pettengill: The Time to Most Recent Common Ancestor Does Not (Usually) Approximate the Date of Divergence, PLOS One, Vol: 10, ISSN: 1932-6203
In 2013 Zhou et al. concluded that Salmonella enterica serovar Agona represents a genetically monomorphic lineage of recent ancestry, whose most recent common ancestor existed in 1932, or earlier. The Abstract stated ‘Agona consists of three lineages with minimal mutational diversity: only 846 single nucleotide polymorphisms (SNPs) have accumulated in the non-repetitive, core genome since Agona evolved in 1932 and subsequently underwent a major population expansion in the 1960s.’ These conclusions have now been criticized by Pettengill, who claims that the evolutionary models used to date Agona may not have been appropriate, the dating estimates were inaccurate, and the age of emergence of Agona should have been qualified by an upper limit reflecting the date of its divergence from an outgroup, serovar Soerenga. We dispute these claims. Firstly, Pettengill’s analysis of Agona is not justifiable on technical grounds. Secondly, an upper limit for divergence from an outgroup would only be meaningful if the outgroup were closely related to Agona, but close relatives of Agona are yet to be identified. Thirdly, it is not possible to reliably date the time of divergence between Agona and Soerenga. We conclude that Pettengill’s criticism is comparable to a tempest in a teapot.
Montano V, Didelot X, Foll M, et al., 2015, Worldwide Population Structure, Long-Term Demography, and Local Adaptation of <i>Helicobacter pylori</i>, GENETICS, Vol: 200, Pages: 947-+, ISSN: 0016-6731
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- Citations: 47
Biek R, Pybus OG, Lloyd-Smith JO, et al., 2015, Measurably evolving pathogens in the genomic era, TRENDS IN ECOLOGY & EVOLUTION, Vol: 30, Pages: 306-313, ISSN: 0169-5347
Current sequencing technologies have created unprecedented opportunities for studying microbial populations. For pathogens with comparatively low per-site mutation rates, such as DNA viruses and bacteria, whole-genome sequencing can reveal the accumulation of novel genetic variation between population samples taken at different times. The concept of ‘measurably evolving populations’ and related analytical approaches have provided powerful insights for fast-evolving RNA viruses, but their application to other pathogens is still in its infancy. We argue that previous distinctions between slow- and fast-evolving pathogens become blurred once evolution is assessed at a genome-wide scale, and we highlight important analytical challenges to be overcome to infer pathogen population dynamics from genomic data.
Cui Y, Yang X, Didelot X, et al., 2015, Epidemic Clones, Oceanic Gene Pools, and Eco-LD in the Free Living Marine Pathogen <i>Vibrio parahaemolyticus</i>, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 32, Pages: 1396-1410, ISSN: 0737-4038
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- Citations: 58
Cao Q, Didelot X, Wu Z, et al., 2015, Progressive genomic convergence of two Helicobacter pylori strains during mixed infection of a patient with chronic gastritis, Gut, Vol: 64, Pages: 554-561, ISSN: 0017-5749
Objective To study the detailed nature of genomic microevolution during mixed infection with multiple Helicobacter pylori strains in an individual. Design We sampled 18 isolates from a single biopsy from a patient with chronic gastritis and nephritis. Whole-genome sequencing was applied to these isolates, and statistical genetic tools were used to investigate their evolutionary history. Results The genomes fall into two clades, reflecting colonisation of the stomach by two distinct strains, and these lineages have accumulated diversity during an estimated 2.8 and 4.2 years of evolution. We detected about 150 clear recombination events between the two clades. Recombination between the lineages is a continuous ongoing process and was detected on both clades, but the effect of recombination in one clade was nearly an order of magnitude higher than in the other. Imputed ancestral sequences also showed evidence of recombination between the two strains prior to their diversification, and we estimate that they have both been infecting the same host for at least 12 years. Recombination tracts between the lineages were, on average, 895 bp in length, and showed evidence for the interspersion of recipient sequences that has been observed in in vitro experiments. The complex evolutionary history of a phage-related protein provided evidence for frequent reinfection of both clades by a single phage lineage during the past 4 years. Conclusions Whole genome sequencing can be used to make detailed conclusions about the mechanisms of genetic change of H. pylori based on sampling bacteria from a single gastric biopsy.
Ezewudo MN, Joseph SJ, Castillo-Ramirez S, et al., 2015, Population structure of <i>Neisseria gonorrhoeae</i> based on whole genome data and its relationship with antibiotic resistance, PEERJ, Vol: 3, ISSN: 2167-8359
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- Citations: 54
Mathers AJ, Stoesser N, Sheppard AE, et al., 2015, <i>Klebsiella pneumoniae</i> Carbapenemase (KPC)-Producing <i>K-pneumoniae</i> at a Single Institution: Insights into Endemicity from Whole-Genome Sequencing, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 59, Pages: 1661-1668, ISSN: 0066-4804
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- Citations: 106
Didelot X, Pang B, Zhou Z, et al., 2015, The Role of China in the Global Spread of the Current Cholera Pandemic, PLOS GENETICS, Vol: 11, ISSN: 1553-7404
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- Citations: 56
Didelot X, Wilson DJ, 2015, ClonalFrameML: Efficient Inference of Recombination in Whole Bacterial Genomes, PLOS COMPUTATIONAL BIOLOGY, Vol: 11, ISSN: 1553-7358
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- Citations: 497
Croucher NJ, Didelot X, 2015, The application of genomics to tracing bacterial pathogen transmission, CURRENT OPINION IN MICROBIOLOGY, Vol: 23, Pages: 62-67, ISSN: 1369-5274
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- Citations: 61
Nandi T, Holden MTG, Didelot X, et al., 2015, <i>Burkholderia pseudomallei</i> sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles, GENOME RESEARCH, Vol: 25, Pages: 129-141, ISSN: 1088-9051
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- Citations: 41
Stoesser N, Giess A, Batty EM, et al., 2014, Genome Sequencing of an Extended Series of NDM-Producing <i>Klebsiella</i> <i>pneumoniae</i> Isolates from Neonatal Infections in a Nepali Hospital Characterizes the Extent of Community- versus Hospital-Associated Transmission in an Endemic Setting, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 58, Pages: 7347-7357, ISSN: 0066-4804
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- Citations: 98
Elliott B, Dingle KE, Didelot X, et al., 2014, The Complexity and Diversity of the Pathogenicity Locus in <i>Clostridium difficile</i> Clade 5, GENOME BIOLOGY AND EVOLUTION, Vol: 6, Pages: 3159-3170, ISSN: 1759-6653
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- Citations: 26
Krebes J, Didelot X, Kennemann L, et al., 2014, Bidirectional genomic exchange between Helicobacter pylori strains from a family in Coventry, United Kingdom, International Journal of Medical Microbiology, Vol: 304, Pages: 1135-1146, ISSN: 1438-4221
The human gastric pathogen Helicobacter pylori is characterised by a high mutation rate and frequent recombination during mixed infection, which result in extensive genetic diversity and rapid allelic diversification. Mixed infections are believed to be much more common in regions with a high H. pylori prevalence than in industrialised countries. To better understand the genomic flexibility of H. pylori in a low prevalence region, we used 454 sequencing technology to investigate whole genome sequences of H. pylori strains isolated from members of three generations of a family living in Coventry, UK. The genomes of four H. pylori strains isolated from a grandfather, two of his sons and one grandson were sequenced. Three of these genomes showed a high overall sequence similarity, suggesting a recent common ancestor. The genomes differed by 316-336 SNPs, and recombination events (imports) resulted in 170-251 clusters of polymorphisms (CNPs). Imports were particularly frequent in genes encoding Helicobacter outer membrane proteins, suggesting an adaptation of the strains to their individual host. The fourth strain differed substantially from these three highly related strains but still shared long fragments of identical sequence, which most likely reflect imports from the highly related family variants. The data show extensive bidirectional exchange of DNA between the strains isolated from the family members, illustrating both the convergence and divergence effect that recombination can lead to. Detailed analysis of the distribution of SNPs and imports permits to draw up a complex scenario of the transmission history involving infection with at least two, and probably more separate strains. This complexity and the resulting high frequency of recombination were unexpected for an industrialised country where the prevalence of H. pylori infection has strongly declined in recent decades.
Didelot X, Gardy J, Colijn C, 2014, Bayesian Inference of Infectious Disease Transmission from Whole-Genome Sequence Data, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 31, Pages: 1869-1879, ISSN: 0737-4038
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- Citations: 135
Yahara K, Didelot X, Ansari MA, et al., 2014, Efficient Inference of Recombination Hot Regions in Bacterial Genomes, MOLECULAR BIOLOGY AND EVOLUTION, Vol: 31, Pages: 1593-1605, ISSN: 0737-4038
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- Citations: 41
Everitt RG, Didelot X, Batty EM, et al., 2014, Mobile elements drive recombination hotspots in the core genome of <i>Staphylococcus aureus</i>, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723
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- Citations: 95
Jombart T, Aanensen DM, Baguelin M, et al., 2014, OutbreakTools: A new platform for disease outbreak analysis using the R software, Epidemics, Vol: 7, Pages: 28-34, ISSN: 1755-4365
The investigation of infectious disease outbreaks relies on the analysis of increasingly complex and diverse data, which offer new prospects for gaining insights into disease transmission processes and informing public health policies. However, the potential of such data can only be harnessed using a number of different, complementary approaches and tools, and a unified platform for the analysis of disease outbreaks is still lacking. In this paper, we present the new R package OutbreakTools, which aims to provide a basis for outbreak data management and analysis in R. OutbreakTools is developed by a community of epidemiologists, statisticians, modellers and bioinformaticians, and implements classes and methods for storing, handling and visualizing outbreak data. It includes real and simulated outbreak datasets. Together with a number of tools for infectious disease epidemiology recently made available in R, OutbreakTools contributes to the emergence of a new, free and open-source platform for the analysis of disease outbreaks.
Haase JK, Didelot X, Lecuit M, et al., 2014, The ubiquitous nature of Listeria monocytogenes clones: A large-scale Multilocus Sequence Typing study, Environmental Microbiology, Vol: 16, Pages: 405-416, ISSN: 1462-2912
Listeria monocytogenes is ubiquitously prevalent in natural environments and is transmitted via the food chain to animals and humans, in whom it can cause life-threatening diseases. We used Multilocus Sequence Typing (MLST) of ~2000 isolates of L.monocytogenes to investigate whether specific associations existed between clonal complexes (CCs) and the environment versus diseased hosts. Most CCs (72%) were not specific for any single source, and many have been isolated from the environment, food products, animals as well as from humans. Our results confirm that the population structure of L.monocytogenes is largely clonal and consists of four lineages (I-IV), three of which contain multiple CCs. Most CCs have remained stable for decades, but one epidemic clone (CC101) was common in the mid-1950s and very rare until recently when it may have begun to re-emerge. The historical perspective used here indicates that the central sequence types of CCs were not ancestral founders but have rather simply increased in frequency over decades. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.
Jombart T, Cori A, Didelot X, et al., 2014, Bayesian Reconstruction of Disease Outbreaks by Combining Epidemiologic and Genomic Data, PLOS COMPUTATIONAL BIOLOGY, Vol: 10, ISSN: 1553-734X
Ansari MA, Didelot X, 2014, Inference of the Properties of the Recombination Process from Whole Bacterial Genomes., Genetics
Patterns of linkage disequilibrium, homoplasy and incompatibility are difficult to interpret because they depend on several factors, including the recombination process and the population structure. Here we introduce a novel model-based framework to infer recombination properties from such summary statistics in bacterial genomes. The underlying model is sequentially Markovian so that data can be simulated very efficiently, and we use approximate Bayesian computation techniques to infer parameters. As this does not require to calculate the likelihood function, the model can be easily extended to investigate less probed aspects of recombination. In particular, we extend our model to account for the bias in the recombination process whereby closely related bacteria recombine more often with one another. We show that this model provides a good fit to a dataset of Bacillus cereus genomes, and estimate several recombination properties, including the rate of bias in recombination. All the methods described in this paper are implemented in a software package which is freely available for download at http://code.google.com/p/clonalorigin/.
O'Brien J, Didelot X, Iqbal Z, et al., 2014, A Bayesian approach to inferring the phylogenetic structure of communities from metagenomic data
Metagenomics provides a powerful new tool set for investigating evolutionaryinteractions with the environment. However, an absence of model-basedstatistical methods means that researchers are often not able to make full useof this complex information. We present a Bayesian method for inferring thephylogenetic relationship among related organisms found within metagenomicsamples. Our approach exploits variation in the frequency of taxa among samplesto simultaneously infer each lineage haplotype, the phylogenetic treeconnecting them, and their frequency within each sample. Applications of thealgorithm to simulated data show that our method can recover a substantialfraction of the phylogenetic structure even in the presence of strong mixingamong samples. We provide examples of the method applied to data from greensulfur bacteria recovered from an Antarctic lake, plastids from mixedPlasmodium falciparum infections, and virulent Neisseria meningitidis samples.
Miller RM, Price JR, Batty EM, et al., 2014, Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: Role of a cryptic variant of an epidemic clone, Journal of Hospital Infection, Vol: 86, Pages: 83-89, ISSN: 0195-6701
Background: New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype. Aim: To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England. Methods: Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains. Findings: By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 × 10-6, Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006. Conclusions: Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms. © 2013 The Authors.
Dingle KE, Elliott B, Robinson E, et al., 2014, Evolutionary History of the <i>Clostridium difficile</i> Pathogenicity Locus, GENOME BIOLOGY AND EVOLUTION, Vol: 6, Pages: 36-52, ISSN: 1759-6653
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- Citations: 126
Krause DJ, Didelot X, Cadillo-Quiroz H, et al., 2014, Recombination Shapes Genome Architecture in an Organism from the Archaeal Domain, GENOME BIOLOGY AND EVOLUTION, Vol: 6, Pages: 170-178, ISSN: 1759-6653
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- Citations: 9
Behrens W, Schweinitzer T, Bal J, et al., 2013, Role of Energy Sensor TlpD of <i>Helicobacter pylori</i> in Gerbil Colonization and Genome Analyses after Adaptation in the Gerbil, INFECTION AND IMMUNITY, Vol: 81, Pages: 3534-3551, ISSN: 0019-9567
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- Citations: 27
Eyre DW, Cule ML, Wilson DJ, et al., 2013, Diverse Sources of <i>C</i>. <i>difficile</i> Infection Identified on Whole-Genome Sequencing, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 369, Pages: 1195-1205, ISSN: 0028-4793
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- Citations: 466
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