Biology subjects

Duchene, S.

Publications and source records attributed to Duchene, S..

8 recordsLinked to original sources

bioRxiv2018

Distinct evolutionary dynamics of horizontal gene transfer in drug resistant and virulent clones of Klebsiella pneumoniae

Klebsiella pneumoniae (Kp) has emerged as an important cause of two distinct public health threats: multidrug resistant (MDR) healthcare-associated infections1 and community-acquired invasive infections, particularly pyogenic liver abscess2. The majority of MDR hospital outbreaks are caused by a subset of Kp clones with a high prevalence of acquired antimicrobial resistance (AMR) genes, while the majority of community-acquired invasive infections are caused by hypervirulent clones that rarely harbour acquired AMR genes but have high prevalence of key virulence loci3-5. Worryingly, the last few years have seen increasing reports of convergence of MDR and the key virulence genes within individual Kp strains6, but it is not yet clear whether these represent a transient phenomenon or a significant ongoing threat. Here we perform comparative genomic analyses for 28 distinct Kp clones, including 6 hypervirulent and 8 MDR, to better understand their evolutionary histories and the risks of convergence. We show that MDR clones are highly diverse with frequent chromosomal recombination and gene content variability that far exceeds that of the hypervirulent clones. Consequently, we predict a much greater risk of virulence gene acquisition by MDR Kp clones than of resistance gene acquisition by hypervirulent clones.

microbiology↗

bioRxiv2018

Phylodynamic model adequacy using posterior predictive simulations

Rapidly evolving pathogens, such as viruses and bacteria, accumulate genetic change at a similar timescale over which their epidemiological processes occur, such that it is possible to make inferences about their infectious spread using phylogenetic time-trees. For this purpose it is necessary to choose a phylodynamic model. However, the resulting inferences are contingent on whether the model adequately describes key features of the data. Model adequacy methods allow formal rejection of a model if it cannot generate the main features of the data. We present TreeModelAdequacy (TMA), a package for the popular BEAST2 software, that allows assessing the adequacy of phylodynamic models. We illustrate its utility by analysing phylogenetic trees from two viral outbreaks of Ebola and H1N1 influenza. The main features of the Ebola data were adequately described by the coalescent exponential-growth model, whereas the H1N1 influenza data was best described by the birth-death SIR model.

bioinformatics↗

bioRxiv2018

Laboratory and Molecular Surveillance of Paediatric Typhoidal Salmonella in Nepal: Antimicrobial Resistance and Implications for Vaccine Policy

BackgroundChildren are substantially affected by enteric fever in most settings with a high burden of the disease, which could be due to immune naivety, or enhanced risk of exposure to the pathogen. Although Nepal is a high burden setting for enteric fever, the bacterial population structure and transmission dynamics are poorly delineated in young children, the proposed target group for immunization programs.\n\nMethodsBlood culture surveillance amongst children aged 2 months to 15 years of age was conducted at Patan Hospital between 2008 and 2016. A total of 198 S. Typhi and 66 S. Paratyphi A isolated from children treated in both inpatient and outpatient settings were subjected to whole genome sequencing and antimicrobial susceptibility testing. Demographic and clinical data were also collected from the inpatients. The resulting data were used to place these paediatric Nepali isolates into a worldwide context, based on their phylogeny and carriage of molecular determinants of antimicrobial resistance (AMR).\n\nResultsChildren aged [≤]4 years made up >40% of the inpatient population. The majority of isolates (78 %) were S. Typhi, comprising several distinct genotypes but dominated by 4.3.1 (H58). Several distinct S. Typhi genotypes were identified, but the globally disseminated S. Typhi clade 4.3.1 (H58) dominated. The majority of isolates (86%) were insusceptible to fluoroquinolones. This was mainly associated with S. Typhi H58 Lineage II and S. Paratyphi A; non-susceptible strains from these two genotypes accounted for 50% and 25% of all enteric fever cases. Multi-drug resistance (MDR) was rare (3.5% of S. Typhi, 0 S. Paratyphi A) and restricted to chromosomal insertions of AMR genes in H58 lineage I strains. Comparison to global data sets showed the local S. Typhi and S. Paratyphi A strains had close genetic relatives in other South Asian countries, indicating regional strain circulation.\n\nConclusionsThese data indicate that enteric fever in Nepal continues to be a major public health issue with ongoing inter- and intra-country transmission, and highlights the need for regional coordination of intervention strategies. The absence of a S. Paratyphi A vaccine is cause for concern, given its prevalence as an enteric fever agent in this setting, and the large proportion of isolates displaying fluoroquinolone resistance. This study also highlights an urgent need for routine laboratory and molecular surveillance to monitor the epidemiology of enteric fever and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions in prevention and control of this febrile illness.

molecular biology↗

bioRxiv2017

Global phylogenomics of multidrug-resistant Staphylococcus aureus sequence type 772: the Bengal Bay clone

The global spread of antimicrobial resistance has been well documented in Gram-negative bacteria and healthcare-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. Here we demonstrate the recent origin and global spread from the Indian subcontinent of a multidrug resistant Staphylococcus aureus lineage, sequence type 772 (Bengal Bay clone). Short-term outbreaks occurred following intercontinental transmission, typically associated with travel and family contacts, but ongoing endemic transmission was uncommon. Instrumental in the emergence of a single dominant clade in the early 1990s was the acquisition of a multidrug resistance integrated plasmid that did not appear to incur a significant fitness cost. The Bengal Bay clone therefore combines the multidrug resistance of traditional healthcare-associated clones with the epidemiological and virulence potential of community-associated clones.

genomics↗

bioRxiv2017

Population genomics of hypervirulent Klebsiella pneumoniae clonal group 23 reveals early emergence and rapid global dissemination

Since the mid-1980s there have been increasing reports of severe community-acquired pyogenic liver abscess, meningitis and bloodstream infections caused by hypervirulent Klebsiella pneumoniae, predominantly encompassing clonal group (CG) 23 serotype K1 strains. Common features of CG23 include a virulence plasmid associated with iron scavenging and hypermucoidy, and a chromosomal integrative and conjugative element (ICE) encoding the siderophore yersiniabactin and the genotoxin colibactin. Here we investigate the evolutionary history and genomic diversity of CG23 based on comparative analysis of 98 genomes. Contrary to previous reports with more limited samples, we show that CG23 comprises several deep branching sublineages dating back to the 1870s, many of which are associated with distinct chromosomal insertions of ICEs encoding yersiniabactin. We find that most liver abscess isolates (>80%) belong to a dominant sublineage, CG23-I, which emerged in the 1920s following acquisition of ICEKp10 (encoding colibactin in addition to yersiniabactin) and has undergone clonal expansion and global dissemination within the human population. The unique genomic feature of CG23-I is the production of colibactin, which has been reported previously as a promoter of gut colonisation and dissemination to the liver and brain in a mouse model of CG23 K. pneumoniae infection, and has been linked to colorectal cancer. We also identify an antibiotic-resistant subclade of CG23-I associated with sexually-transmitted infections in horses dating back to the 1980s. These data show that hypervirulent CG23 K. pneumoniae was circulating in humans for decades before the liver abscess epidemic was first recognised, and has the capacity to acquire and maintain AMR plasmids. These data provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To further support such studies we present an open access and completely sequenced human liver abscess isolate, SGH10, which is typical of the globally disseminated CG23-I sublineage.

genomics↗

bioRxiv2017

Inferring demographic parameters in bacterial genomic data using Bayesian and hybrid phylogenetic methods

BackgroundRecent developments in sequencing technologies make it possible to obtain genome sequences from a large number of isolates in a very short time. Bayesian phylogenetic approaches can take advantage of these data by simultaneously inferring the phylogenetic tree, evolutionary timescale, and demographic parameters (such as population growth rates), while naturally integrating uncertainty in all parameters. Despite their desirable properties, Bayesian approaches can be computationally intensive, hindering their use for outbreak investigations involving genome data for a large numbers of pathogen isolates. An alternative to using full Bayesian inference is to use a hybrid approach, where the phylogenetic tree and evolutionary timescale are estimated first using maximum likelihood. Under this hybrid approach, demographic parameters are inferred from estimated trees instead of the sequence data, using maximum likelihood, Bayesian inference, or approximate Bayesian computation. This can vastly reduce the computational burden, but has the disadvantage of ignoring the uncertainty in the phylogenetic tree and evolutionary timescale.\n\nResultsWe compared the performance of a fully Bayesian and a hybrid method by analysing six whole-genome SNP data sets from a range of bacteria and simulations. The estimates from the two methods were very similar, suggesting that the hybrid method is a valid alternative for very large datasets. However, we also found that congruence between these methods is contingent on the presence of strong temporal structure in the data (i.e. clocklike behaviour), which is typically verified using a date-randomisation test in a Bayesian framework. To reduce the computational burden of this Bayesian test we implemented a date-randomisation test using a rapid maximum likelihood method, which has similar performance to its Bayesian counterpart.\n\nConclusionsHybrid approaches can produce reliable inferences of evolutionary timescales and phylodynamic parameters in a fraction of the time required for fully Bayesian analyses. As such, they are a valuable alternative in outbreak studies involving a large number of isolates.

bioinformatics↗

bioRxiv2017

A Comparison of Methods for Estimating Substitution Rates from Ancient DNA Sequence Data

The estimation of evolutionary rates from ancient DNA sequences can be negatively affected by among-lineage rate variation and non-random sampling. Using a simulation study, we compared the performance of three phylogenetic methods for inferring evolutionary rates from time-structured data sets: root-to-tip regression, least-squares dating, and Bayesian inference. Our results show that these methods produce reliable estimates when the substitution rate is high, rate variation is low, and samples of similar ages are not phylogenetically clustered. The interaction of these factors is particularly important for Bayesian estimation of evolutionary rates. We also inferred rates for time-structured mitogenomic data sets from six vertebrate species. Root-to-tip regression estimated a different rate from least-squares dating and Bayesian inference for mitogenomes from the horse, which has high levels of among-lineage rate variation. We recommend using multiple methods of inference and testing data for temporal signal, among-lineage rate variation, and phylo-temporal clustering.

evolutionary biology↗

bioRxiv2017

Millennia of genomic stability within the invasive Para C Lineage of Salmonella enterica

Salmonella enterica serovar Paratyphi C is the causative agent of enteric (paratyphoid) fever. While today a potentially lethal infection of humans that occurs in Africa and Asia, early 20th century observations in Eastern Europe suggest it may once have had a wider-ranging impact on human societies. We recovered a draft Paratyphi C genome from the 800-year-old skeleton of a young woman in Trondheim, Norway, who likely died of enteric fever. Analysis of this genome against a new, significantly expanded database of related modern genomes demonstrated that Paratyphi C is descended from the ancestors of swine pathogens, serovars Choleraesuis and Typhisuis, together forming the Para C Lineage. Our results indicate that Paratyphi C has been a pathogen of humans for at least 1,000 years, and may have evolved after zoonotic transfer from swine during the Neolithic period.\n\nOne Sentence SummaryThe combination of an 800-year-old Salmonella enterica Paratyphi C genome with genomes from extant bacteria reshapes our understanding of this pathogens origins and evolution.

microbiology↗