Publications by authors named "Sebastian Duchene"

72 Publications

The Impacts of Low Diversity Sequence Data on Phylodynamic Inference during an Emerging Epidemic.

Viruses 2021 Jan 8;13(1). Epub 2021 Jan 8.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC 3010, Australia.

Phylodynamic inference is a pivotal tool in understanding transmission dynamics of viral outbreaks. These analyses are strongly guided by the input of an epidemiological model as well as sequence data that must contain sufficient intersequence variability in order to be informative. These criteria, however, may not be met during the early stages of an outbreak. Here we investigate the impact of low diversity sequence data on phylodynamic inference using the birth-death and coalescent exponential models. Through our simulation study, estimating the molecular evolutionary rate required enough sequence diversity and is an essential first step for any phylodynamic inference. Following this, the birth-death model outperforms the coalescent exponential model in estimating epidemiological parameters, when faced with low diversity sequence data due to explicitly exploiting the sampling times. In contrast, the coalescent model requires additional samples and therefore variability in sequence data before accurate estimates can be obtained. These findings were also supported through our empirical data analyses of an Australian and a New Zealand cluster outbreaks of SARS-CoV-2. Overall, the birth-death model is more robust when applied to datasets with low sequence diversity given sampling is specified and this should be considered for future viral outbreak investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13010079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826997PMC
January 2021

Genomic Epidemiology of the First Wave of SARS-CoV-2 in Italy.

Viruses 2020 12 14;12(12). Epub 2020 Dec 14.

Istituto Zooprofilattico Sperimentale dell'Abruzzo e del Molise G. Caporale, 641000 Teramo, Italy.

Italy was one of the first countries to experience a major epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with >1000 cases confirmed by 1 March 2020. However, virus genome sequence data is sparse and there has been only limited investigation of virus transmission across the country. Here, we provide the most extensive study to date of the genomic epidemiology of SARS-CoV-2 in Italy covering the first wave of infection. We generated 191 new full-length genomes, largely sampled from central Italy (Abruzzo), before, during, and after the enforcement of a nationwide "lockdown" (8 March-3 June). These were combined with 460 published SARS-CoV-2 sequences sampled across Italy. Phylogenetic analysis including global sequence data revealed multiple independent introductions into Italy, with at least 124 instances of sequence clusters representing longer chains of transmission. Eighteen of these transmission clusters emerged before the nation-wide lockdown was implemented on 8 March, and an additional 18 had evidence for transmission between different Italian regions. Extended transmission periods between infections of up to 104 days were observed in five clusters. In addition, we found seven clusters that persisted throughout the lockdown period. Overall, we show how importations were an important driver of the first wave of SARS-CoV-2 in Italy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v12121438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765063PMC
December 2020

Genomic epidemiology reveals transmission patterns and dynamics of SARS-CoV-2 in Aotearoa New Zealand.

Nat Commun 2020 12 11;11(1):6351. Epub 2020 Dec 11.

Institute of Environmental Science and Research, Wellington, New Zealand.

New Zealand, a geographically remote Pacific island with easily sealable borders, implemented a nationwide 'lockdown' of all non-essential services to curb the spread of COVID-19. Here, we generate 649 SARS-CoV-2 genome sequences from infected patients in New Zealand with samples collected during the 'first wave', representing 56% of all confirmed cases in this time period. Despite its remoteness, the viruses imported into New Zealand represented nearly all of the genomic diversity sequenced from the global virus population. These data helped to quantify the effectiveness of public health interventions. For example, the effective reproductive number, R of New Zealand's largest cluster decreased from 7 to 0.2 within the first week of lockdown. Similarly, only 19% of virus introductions into New Zealand resulted in ongoing transmission of more than one additional case. Overall, these results demonstrate the utility of genomic pathogen surveillance to inform public health and disease mitigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-20235-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733492PMC
December 2020

Temporal signal and the phylodynamic threshold of SARS-CoV-2.

Virus Evol 2020 Jul 19;6(2):veaa061. Epub 2020 Aug 19.

Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.

The ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus's evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at eight different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by 2 February 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 and 122 genomes, converged at an evolutionary rate of about 1.1 × 10 subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ve/veaa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454936PMC
July 2020

The Recovery, Interpretation and Use of Ancient Pathogen Genomes.

Curr Biol 2020 Oct;30(19):R1215-R1231

McMaster Ancient DNA Centre, Departments of Anthropology and Biochemistry, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4L9, Canada; Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, 1280 Main St. W., Hamilton, ON L8S 4L8, Canada; Humans and the Microbiome Program, Canadian Institute for Advanced Research, Toronto, Canada. Electronic address:

The ability to sequence genomes from ancient biological material has provided a rich source of information for evolutionary biology and engaged considerable public interest. Although most studies of ancient genomes have focused on vertebrates, particularly archaic humans, newer technologies allow the capture of microbial pathogens and microbiomes from ancient and historical human and non-human remains. This coming of age has been made possible by techniques that allow the preferential capture and amplification of discrete genomes from a background of predominantly host and environmental DNA. There are now near-complete ancient genome sequences for three pathogens of considerable historical interest - pre-modern bubonic plague (Yersinia pestis), smallpox (Variola virus) and cholera (Vibrio cholerae) - and for three equally important endemic human disease agents - Mycobacterium tuberculosis (tuberculosis), Mycobacterium leprae (leprosy) and Treponema pallidum pallidum (syphilis). Genomic data from these pathogens have extended earlier work by paleopathologists. There have been efforts to sequence the genomes of additional ancient pathogens, with the potential to broaden our understanding of the infectious disease burden common to past populations from the Bronze Age to the early 20 century. In this review we describe the state-of-the-art of this rapidly developing field, highlight the contributions of ancient pathogen genomics to multidisciplinary endeavors and describe some of the limitations in resolving questions about the emergence and long-term evolution of pathogens.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2020.08.081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534838PMC
October 2020

Bayesian Evaluation of Temporal Signal in Measurably Evolving Populations.

Mol Biol Evol 2020 11;37(11):3363-3379

Department of Microbiology, Immunology and Transplantation, Rega Institute, KU Leuven, Leuven, Belgium.

Phylogenetic methods can use the sampling times of molecular sequence data to calibrate the molecular clock, enabling the estimation of evolutionary rates and timescales for rapidly evolving pathogens and data sets containing ancient DNA samples. A key aspect of such calibrations is whether a sufficient amount of molecular evolution has occurred over the sampling time window, that is, whether the data can be treated as having come from a measurably evolving population. Here, we investigate the performance of a fully Bayesian evaluation of temporal signal (BETS) in sequence data. The method involves comparing the fit to the data of two models: a model in which the data are accompanied by the actual (heterochronous) sampling times, and a model in which the samples are constrained to be contemporaneous (isochronous). We conducted simulations under a wide range of conditions to demonstrate that BETS accurately classifies data sets according to whether they contain temporal signal or not, even when there is substantial among-lineage rate variation. We explore the behavior of this classification in analyses of five empirical data sets: modern samples of A/H1N1 influenza virus, the bacterium Bordetella pertussis, coronaviruses from mammalian hosts, ancient DNA from Hepatitis B virus, and mitochondrial genomes of dog species. Our results indicate that BETS is an effective alternative to other tests of temporal signal. In particular, this method has the key advantage of allowing a coherent assessment of the entire model, including the molecular clock and tree prior which are essential aspects of Bayesian phylodynamic analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/molbev/msaa163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454806PMC
November 2020

Tracking the COVID-19 pandemic in Australia using genomics.

Nat Commun 2020 09 1;11(1):4376. Epub 2020 Sep 1.

Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.

Genomic sequencing has significant potential to inform public health management for SARS-CoV-2. Here we report high-throughput genomics for SARS-CoV-2, sequencing 80% of cases in Victoria, Australia (population 6.24 million) between 6 January and 14 April 2020 (total 1,333 COVID-19 cases). We integrate epidemiological, genomic and phylodynamic data to identify clusters and impact of interventions. The global diversity of SARS-CoV-2 is represented, consistent with multiple importations. Seventy-six distinct genomic clusters were identified, including large clusters associated with social venues, healthcare and cruise ships. Sequencing sequential samples from 98 patients reveals minimal intra-patient SARS-CoV-2 genomic diversity. Phylodynamic modelling indicates a significant reduction in the effective viral reproductive number (R) from 1.63 to 0.48 after implementing travel restrictions and physical distancing. Our data provide a concrete framework for the use of SARS-CoV-2 genomics in public health responses, including its use to rapidly identify SARS-CoV-2 transmission chains, increasingly important as social restrictions ease globally.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-020-18314-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462846PMC
September 2020

Dating the emergence of human pathogens.

Science 2020 06;368(6497):1310-1311

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abc5746DOI Listing
June 2020

Linking Branch Lengths across Sets of Loci Provides the Highest Statistical Support for Phylogenetic Inference.

Mol Biol Evol 2020 04;37(4):1202-1210

School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.

Evolution leaves heterogeneous patterns of nucleotide variation across the genome, with different loci subject to varying degrees of mutation, selection, and drift. In phylogenetics, the potential impacts of partitioning sequence data for the assignment of substitution models are well appreciated. In contrast, the treatment of branch lengths has received far less attention. In this study, we examined the effects of linking and unlinking branch-length parameters across loci or subsets of loci. By analyzing a range of empirical data sets, we find consistent support for a model in which branch lengths are proportionate between subsets of loci: gene trees share the same pattern of branch lengths, but form subsets that vary in their overall tree lengths. These models had substantially better statistical support than models that assume identical branch lengths across gene trees, or those in which genes form subsets with distinct branch-length patterns. We show using simulations and empirical data that the complexity of the branch-length model with the highest support depends on the length of the sequence alignment and on the numbers of taxa and loci in the data set. Our findings suggest that models in which branch lengths are proportionate between subsets have the highest statistical support under the conditions that are most commonly seen in practice. The results of our study have implications for model selection, computational efficiency, and experimental design in phylogenomics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/molbev/msz291DOI Listing
April 2020

Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent.

mBio 2019 11 26;10(6). Epub 2019 Nov 26.

Menzies School of Health Research, Darwin, Australia

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-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. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere. The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.01105-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879714PMC
November 2019

The molecular clock of Mycobacterium tuberculosis.

PLoS Pathog 2019 09 12;15(9):e1008067. Epub 2019 Sep 12.

Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.

The molecular clock and its phylogenetic applications to genomic data have changed how we study and understand one of the major human pathogens, Mycobacterium tuberculosis (MTB), the etiologic agent of tuberculosis. Genome sequences of MTB strains sampled at different times are increasingly used to infer when a particular outbreak begun, when a drug-resistant clone appeared and expanded, or when a strain was introduced into a specific region. Despite the growing importance of the molecular clock in tuberculosis research, there is a lack of consensus as to whether MTB displays a clocklike behavior and about its rate of evolution. Here we performed a systematic study of the molecular clock of MTB on a large genomic data set (6,285 strains), covering different epidemiological settings and most of the known global diversity. We found that sampling times below 15-20 years were often insufficient to calibrate the clock of MTB. For data sets where such calibration was possible, we obtained a clock rate between 1x10-8 and 5x10-7 nucleotide changes per-site-per-year (0.04-2.2 SNPs per-genome-per-year), with substantial differences between clades. These estimates were not strongly dependent on the time of the calibration points as they changed only marginally when we used epidemiological isolates (sampled in the last 40 years) or three ancient DNA samples (about 1,000 years old) to calibrate the tree. Additionally, the uncertainty and the discrepancies in the results of different methods were sometimes large, highlighting the importance of using different methods, and of considering carefully their assumptions and limitations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.ppat.1008067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759198PMC
September 2019

Limited Sustained Local Transmission of HIV-1 CRF01_AE in New South Wales, Australia.

Viruses 2019 05 27;11(5). Epub 2019 May 27.

The Kirby Institute, The University of New South Wales, Sydney, New South Wales 2052, Australia.

Australia's response to the human immunodeficiency virus type 1 (HIV-1) pandemic led to effective control of HIV transmission and one of the world's lowest HIV incidence rates-0.14%. Although there has been a recent decline in new HIV diagnoses in New South Wales (NSW), the most populous state in Australia, there has been a concomitant increase with non-B subtype infections, particularly for the HIV-1 circulating recombinant form CRF01_AE. This aforementioned CRF01_AE sampled in NSW, were combined with those sampled globally to identify NSW-specific viral clades. The population growth of these clades was assessed in two-year period intervals from 2009 to 2017. Overall, 109 NSW-specific clades were identified, most comprising pairs of sequences; however, five large clades comprising ≥10 sequences were also found. Forty-four clades grew over time with one or two sequences added to each in different two-year periods. Importantly, while 10 of these clades have seemingly discontinued, the remaining 34 were still active in 2016/2017. Seven such clades each comprised ≥10 sequences, and are representative of individual sub-epidemics in NSW. Thus, although the majority of new CRF01_AE infections were associated with small clades that rarely establish ongoing chains of local transmission, individual sub-epidemics are present and should be closely monitored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v11050482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563510PMC
May 2019

Genome Analysis of Coxsackievirus A4 Isolates From Hand, Foot, and Mouth Disease Cases in Shandong, China.

Front Microbiol 2019 7;10:1001. Epub 2019 May 7.

Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Tai'an, China.

Coxsackievirus A4 (CVA4) is one of the most prevalent pathogens associated with hand, foot and mouth disease (HFMD), an acute febrile illness in children, and is also associated with acute localized exanthema, myocarditis, hepatitis and pancreatitis. Despite this, limited CVA4 genome sequences are currently available. Herein, complete genome sequences from CVA4 strains ( = 21), isolated from patients with HFMD in Shandong province, China between 2014 and 2016, were determined and phylogenetically characterized. Phylogenetic analysis of the gene from a larger CVA4 collection ( = 175) showed that CVA4 has evolved into four separable genotypes: A, B, C, and D; and genotype D could be further classified in to two sub-genotypes: D1 and D2. Each of the 21 newly described genomes derived from isolates that segregated with sub-genotype D2. The CVA4 genomes displayed significant intra-genotypic genetic diversity with frequent synonymous substitutions occurring at the third codon positions, particularly within the P2 region. However, was relatively stable and therefore represents a potential target for molecular diagnostics assays and also for the rational design of vaccine epitopes. The substitution rate of was estimated to be 5.12 × 10 substitutions/site/year, indicative of ongoing CVA4 evolution. Mutations at amino acid residue 169 in gene may be responsible for differing virulence of CVA4 strains. Bayesian skyline plot analysis showed that the population size of CVA4 has experienced several dynamic fluctuations since 1948. In summary, we describe the phylogenetic and molecular characterization of 21 complete genomes from CVA4 isolates which greatly enriches the known genomic diversity of CVA4 and underscores the need for further surveillance of CVA4 in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2019.01001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6513881PMC
May 2019

Atlas of group A streptococcal vaccine candidates compiled using large-scale comparative genomics.

Nat Genet 2019 06 27;51(6):1035-1043. Epub 2019 May 27.

School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.

Group A Streptococcus (GAS; Streptococcus pyogenes) is a bacterial pathogen for which a commercial vaccine for humans is not available. Employing the advantages of high-throughput DNA sequencing technology to vaccine design, we have analyzed 2,083 globally sampled GAS genomes. The global GAS population structure reveals extensive genomic heterogeneity driven by homologous recombination and overlaid with high levels of accessory gene plasticity. We identified the existence of more than 290 clinically associated genomic phylogroups across 22 countries, highlighting challenges in designing vaccines of global utility. To determine vaccine candidate coverage, we investigated all of the previously described GAS candidate antigens for gene carriage and gene sequence heterogeneity. Only 15 of 28 vaccine antigen candidates were found to have both low naturally occurring sequence variation and high (>99%) coverage across this diverse GAS population. This technological platform for vaccine coverage determination is equally applicable to prospective GAS vaccine antigens identified in future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0417-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6650292PMC
June 2019

Can Sequence Phylogenies Safely Infer the Origin of the Global Virome?

mBio 2019 04 16;10(2). Epub 2019 Apr 16.

Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/mBio.00289-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6469966PMC
April 2019

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

PLoS Genet 2019 04 15;15(4):e1008114. Epub 2019 Apr 15.

Department of Infectious Diseases, Monash University, Melbourne, Victoria, Australia.

Klebsiella pneumoniae has emerged as an important cause of two distinct public health threats: multi-drug resistant (MDR) healthcare-associated infections and drug susceptible community-acquired invasive infections. These pathotypes are generally associated with two distinct subsets of K. pneumoniae lineages or 'clones' that are distinguished by the presence of acquired resistance genes and several key virulence loci. Genomic evolutionary analyses of the most notorious MDR and invasive community-associated ('hypervirulent') clones indicate differences in terms of chromosomal recombination dynamics and capsule polysaccharide diversity, but it remains unclear if these differences represent generalised trends. Here we leverage a collection of >2200 K. pneumoniae genomes to identify 28 common clones (n ≥ 10 genomes each), and perform the first genomic evolutionary comparison. Eight MDR and 6 hypervirulent clones were identified on the basis of acquired resistance and virulence gene prevalence. Chromosomal recombination, surface polysaccharide locus diversity, pan-genome, plasmid and phage dynamics were characterised and compared. The data showed that MDR clones were highly diverse, with frequent chromosomal recombination generating extensive surface polysaccharide locus diversity. Additional pan-genome diversity was driven by frequent acquisition/loss of both plasmids and phage. In contrast, chromosomal recombination was rare in the hypervirulent clones, which also showed a significant reduction in pan-genome diversity, largely driven by a reduction in plasmid diversity. Hence the data indicate that hypervirulent clones may be subject to some sort of constraint for horizontal gene transfer that does not apply to the MDR clones. Our findings are relevant for understanding the risk of emergence of individual K. pneumoniae strains carrying both virulence and acquired resistance genes, which have been increasingly reported and cause highly virulent infections that are extremely difficult to treat. Specifically, our data indicate that MDR clones pose the greatest risk, because they are more likely to acquire virulence genes than hypervirulent clones are to acquire resistance genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1008114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483277PMC
April 2019

BEAST 2.5: An advanced software platform for Bayesian evolutionary analysis.

PLoS Comput Biol 2019 04 8;15(4):e1006650. Epub 2019 Apr 8.

Centre of Computational Evolution, University of Auckland, Auckland, New Zealand.

Elaboration of Bayesian phylogenetic inference methods has continued at pace in recent years with major new advances in nearly all aspects of the joint modelling of evolutionary data. It is increasingly appreciated that some evolutionary questions can only be adequately answered by combining evidence from multiple independent sources of data, including genome sequences, sampling dates, phenotypic data, radiocarbon dates, fossil occurrences, and biogeographic range information among others. Including all relevant data into a single joint model is very challenging both conceptually and computationally. Advanced computational software packages that allow robust development of compatible (sub-)models which can be composed into a full model hierarchy have played a key role in these developments. Developing such software frameworks is increasingly a major scientific activity in its own right, and comes with specific challenges, from practical software design, development and engineering challenges to statistical and conceptual modelling challenges. BEAST 2 is one such computational software platform, and was first announced over 4 years ago. Here we describe a series of major new developments in the BEAST 2 core platform and model hierarchy that have occurred since the first release of the software, culminating in the recent 2.5 release.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pcbi.1006650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472827PMC
April 2019

Tracing Ancient Human Migrations into Sahul Using Hepatitis B Virus Genomes.

Mol Biol Evol 2019 05;36(5):942-954

Victorian Infectious Diseases Reference Laboratory, The Royal Melbourne Hospital, at the Doherty Institute, Melbourne, Australia.

The entry point and timing of ancient human migration into continental Sahul (the combined landmass of Australia, New Guinea, and Tasmania) are subject to debate. Unique strains of hepatitis B virus (HBV) are endemic among modern-day Australian Aboriginals (HBV/C4) and Indigenous Melanesians (HBV/C3). We postulated that HBV genomes could be used to infer human population movements because the main HBV transmission route in endemic populations is via mother-to-child for genotypes B and C infections. Phylogenetic and phylogeographic analyses of HBV genomes inferred the origin of HBV/C4 to be >59 thousand years ago (ka) (95% HPD: 34-85 ka), and most likely to have occurred on the Sunda Shelf (southeast extension of the continental shelf of Southeast Asia). Our analysis further suggested an age of >51 ka (95% Highest Posterior Density (HPD): 36-67 ka) for the most recent common ancestor of HBV/C4 in Australia, correlating with the arrival time of anatomically modern humans into Australia, with the entry point suggested along a southern route via Timor. While we also inferred the origin of HBC/C3 to be on the Sunda Shelf, our analyses suggested that it was carried into Melanesia by Indigenous Melanesians who migrated through New Guinea north of the highlands. These findings reveal that HBV genomes can be used to infer ancient human population movements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/molbev/msz021DOI Listing
May 2019

Evolutionary stasis of viruses?

Nat Rev Microbiol 2019 05;17(5):329

Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41579-019-0168-7DOI Listing
May 2019

The Asian Lineage of Zika Virus: Transmission and Evolution in Asia and the Americas.

Virol Sin 2019 Feb 25;34(1):1-8. Epub 2019 Jan 25.

Key Laboratory of Etiology and Epidemiology of Emerging Infectious Diseases in Universities of Shandong, Taishan Medical College, Taian, 271000, China.

Since first isolation in 1947 from the Zika forest in Uganda, Zika virus (ZIKV) has been principally known as a benign agent associated with sporadic human infections in a restricted number of African countries. However, during 2015-2016, an Asian lineage of ZIKV caused an unprecedentedly large outbreak in the Americas and sizeable numbers of exported cases across the globe. In this review, we critically appraise the recent advances in molecular epidemiological studies of ZIKV performed to date, and we highlight the pivotal role played by genomic surveillance in elucidating the origins, dissemination and evolution of the Asian lineage of ZIKV in Asia and in the Americas.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12250-018-0078-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420435PMC
February 2019

The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa.

Nat Commun 2018 11 30;9(1):5094. Epub 2018 Nov 30.

The Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, 764 Vo Van Kiet, Quant 5, Ho Chi Minh City, Vietnam.

There is paucity of data regarding the geographical distribution, incidence, and phylogenetics of multi-drug resistant (MDR) Salmonella Typhi in sub-Saharan Africa. Here we present a phylogenetic reconstruction of whole genome sequenced 249 contemporaneous S. Typhi isolated between 2008-2015 in 11 sub-Saharan African countries, in context of the 2,057 global S. Typhi genomic framework. Despite the broad genetic diversity, the majority of organisms (225/249; 90%) belong to only three genotypes, 4.3.1 (H58) (99/249; 40%), 3.1.1 (97/249; 39%), and 2.3.2 (29/249; 12%). Genotypes 4.3.1 and 3.1.1 are confined within East and West Africa, respectively. MDR phenotype is found in over 50% of organisms restricted within these dominant genotypes. High incidences of MDR S. Typhi are calculated in locations with a high burden of typhoid, specifically in children aged <15 years. Antimicrobial stewardship, MDR surveillance, and the introduction of typhoid conjugate vaccines will be critical for the control of MDR typhoid in Africa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-07370-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269545PMC
November 2018

Pan-genome Analysis of Ancient and Modern Salmonella enterica Demonstrates Genomic Stability of the Invasive Para C Lineage for Millennia.

Curr Biol 2018 08 19;28(15):2420-2428.e10. Epub 2018 Jul 19.

Warwick Medical School, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. Electronic address:

Salmonella enterica serovar Paratyphi C causes enteric (paratyphoid) fever in humans. Its presentation can range from asymptomatic infections of the blood stream to gastrointestinal or urinary tract infection or even a fatal septicemia [1]. Paratyphi C is very rare in Europe and North America except for occasional travelers from South and East Asia or Africa, where the disease is more common [2, 3]. However, early 20-century observations in Eastern Europe [3, 4] suggest that Paratyphi C enteric fever may once have had a wide-ranging impact on human societies. Here, we describe a draft Paratyphi C genome (Ragna) recovered from the 800-year-old skeleton (SK152) of a young woman in Trondheim, Norway. Paratyphi C sequences were recovered from her teeth and bones, suggesting that she died of enteric fever and demonstrating that these bacteria have long caused invasive salmonellosis in Europeans. Comparative analyses against modern Salmonella genome sequences revealed that Paratyphi C is a clade within the Para C lineage, which also includes serovars Choleraesuis, Typhisuis, and Lomita. Although Paratyphi C only infects humans, Choleraesuis causes septicemia in pigs and boar [5] (and occasionally humans), and Typhisuis causes epidemic swine salmonellosis (chronic paratyphoid) in domestic pigs [2, 3]. These different host specificities likely evolved in Europe over the last ∼4,000 years since the time of their most recent common ancestor (tMRCA) and are possibly associated with the differential acquisitions of two genomic islands, SPI-6 and SPI-7. The tMRCAs of these bacterial clades coincide with the timing of pig domestication in Europe [6].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cub.2018.05.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089836PMC
August 2018

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

Nat Commun 2018 07 13;9(1):2703. Epub 2018 Jul 13.

Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, 3010, Australia.

Severe liver abscess infections caused by hypervirulent clonal-group CG23 Klebsiella pneumoniae have been increasingly reported since the mid-1980s. Strains typically possess several virulence factors including an integrative, conjugative element ICEKp encoding the siderophore yersiniabactin and genotoxin colibactin. Here we investigate CG23's evolutionary history, showing several deep-branching sublineages associated with distinct ICEKp acquisitions. Over 80% of liver abscess isolates belong to sublineage CG23-I, which emerged in ~1928 following acquisition of ICEKp10 (encoding yersiniabactin and colibactin), and then disseminated globally within the human population. CG23-I's distinguishing feature is the colibactin synthesis locus, which reportedly promotes gut colonisation and metastatic infection in murine models. These data show circulation of CG23 K. pneumoniae decades before the liver abscess epidemic was first recognised, and provide a framework for future epidemiological and experimental studies of hypervirulent K. pneumoniae. To support such studies we present an open access, completely sequenced CG23-I human liver abscess isolate, SGH10.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-05114-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6045662PMC
July 2018

Phylodynamic Model Adequacy Using Posterior Predictive Simulations.

Syst Biol 2019 03;68(2):358-364

Centre for Computational Evolution, University of Auckland, Auckland, New Zealand.

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, a package for the popular BEAST2 software that allows assessing the adequacy of phylodynamic models. We illustrate its utility by analyzing 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 were best described by the birth-death susceptible-infected-recovered model.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/sysbio/syy048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6368481PMC
March 2019

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

BMC Evol Biol 2018 06 19;18(1):95. Epub 2018 Jun 19.

Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, 3020, Australia.

Background: Recent 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.

Results: We 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.

Conclusions: Hybrid 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12862-018-1210-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006949PMC
June 2018

Differences in Performance among Test Statistics for Assessing Phylogenomic Model Adequacy.

Genome Biol Evol 2018 06;10(6):1375-1388

School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia.

Statistical phylogenetic analyses of genomic data depend on models of nucleotide or amino acid substitution. The adequacy of these substitution models can be assessed using a number of test statistics, allowing the model to be rejected when it is found to provide a poor description of the evolutionary process. A potentially valuable use of model-adequacy test statistics is to identify when data sets are likely to produce unreliable phylogenetic estimates, but their differences in performance are rarely explored. We performed a comprehensive simulation study to identify test statistics that are sensitive to some of the most commonly cited sources of phylogenetic estimation error. Our results show that, for many test statistics, traditional thresholds for assessing model adequacy can fail to reject the model when the phylogenetic inferences are inaccurate and imprecise. This is particularly problematic when analysing loci that have few informative sites. We propose new thresholds for assessing substitution model adequacy and demonstrate their effectiveness in analyses of three phylogenomic data sets. These thresholds lead to frequent rejection of the model for loci that yield topological inferences that are imprecise and are likely to be inaccurate. We also propose the use of a summary statistic that provides a practical assessment of overall model adequacy. Our approach offers a promising means of enhancing model choice in genome-scale data sets, potentially leading to improvements in the reliability of phylogenomic inference.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/gbe/evy094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6007652PMC
June 2018

A comparison of methods for estimating substitution rates from ancient DNA sequence data.

BMC Evol Biol 2018 05 16;18(1):70. Epub 2018 May 16.

School of Life and Environmental Sciences, University of Sydney, Sydney, Australia.

Background: Phylogenetic analysis of DNA from modern and ancient samples allows the reconstruction of important demographic and evolutionary processes. A critical component of these analyses is the estimation of evolutionary rates, which can be calibrated using information about the ages of the samples. However, the reliability of these rate estimates 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: regression of root-to-tip distances, least-squares dating, and Bayesian inference. We also applied these three methods to time-structured mitogenomic data sets from six vertebrate species.

Results: Our results from 12 simulation scenarios show that the three methods produce reliable estimates when the substitution rate is high, rate variation is low, and samples of similar ages are not all grouped together in the tree (i.e., low phylo-temporal clustering). The interaction of these factors is particularly important for least-squares dating and Bayesian estimation of evolutionary rates. The three estimation methods produced consistent estimates of rates across most of the six mitogenomic data sets, with sequence data from horses being an exception.

Conclusions: We recommend that phylogenetic studies of ancient DNA sequences should use multiple methods of inference and test for the presence of temporal signal, among-lineage rate variation, and phylo-temporal clustering in the data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12862-018-1192-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956955PMC
May 2018

Laboratory and molecular surveillance of paediatric typhoidal Salmonella in Nepal: Antimicrobial resistance and implications for vaccine policy.

PLoS Negl Trop Dis 2018 04 23;12(4):e0006408. Epub 2018 Apr 23.

Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.

Background: Children are substantially affected by enteric fever in most settings with a high burden of the disease, including Nepal. However pathogen population structure and transmission dynamics are poorly delineated in young children, the proposed target group for immunization programs. Here we present whole genome sequencing and antimicrobial susceptibility data on 198 S. Typhi and 66 S. Paratyphi A isolated from children aged 2 months to 15 years of age during blood culture surveillance at Patan Hospital, Nepal, 2008-2016.

Principal Findings: S. Typhi was the dominant agent and comprised several distinct genotypes, dominated by 4.3.1 (H58). The heterogeneity of genotypes in children under five was reduced compared to data from 2005-2006, attributable to ongoing clonal expansion of H58. Most isolates (86%) were non-susceptible to fluoroquinolones, associated mainly with S. Typhi H58 lineage II and S. Paratyphi A harbouring mutations in the quinolone resistance-determining region (QRDR); non-susceptible strains from these groups accounted for 50% and 25% of all isolates. Multi-drug resistance (MDR) was rare (3.5% of S. Typhi, 0 S. Paratyphi A) and restricted to chromosomal insertions of resistance genes in H58 lineage I strains. Temporal analyses revealed a shift in dominance from H58 Lineage I to H58 Lineage II, with the latter being significantly more common after 2010. 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. Multiple imports from India of ciprofloxacin-resistant H58 lineage II strains were identified, but these were rare and showed no evidence of clonal replacement of local S. Typhi.

Significance: These 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 a fluoroquinolone resistant enteric fever agent in this setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0006408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933809PMC
April 2018

Estimating evolutionary rates in giant viruses using ancient genomes.

Virus Evol 2018 Jan 27;4(1):vey006. Epub 2018 Feb 27.

Marie Bashir Institute of Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Life and Environmental Sciences and Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia.

is a giant (610 Kpb) double-stranded DNA virus discovered in a purportedly 30,000-year-old permafrost sample. A closely related virus, , was recently isolated from a sewer in southern France. An initial comparison of these two virus genomes assumed that was directly ancestral to and gave a maximum evolutionary rate of 2.60 × 10 nucleotide substitutions per site per year (subs/site/year). If correct, this would make pithoviruses among the fastest-evolving DNA viruses, with rates close to those seen in some RNA viruses. To help determine whether this unusually high rate is accurate we utilized the well-known negative association between evolutionary rate and genome size in DNA microbes. This revealed that a more plausible rate estimate for evolution is ∼2.23 × 10 subs/site/year, with even lower estimates obtained if evolutionary rates are assumed to be time-dependent. Hence, we estimate that has evolved at least an order of magnitude more slowly than previously suggested. We then used our new rate estimates to infer a time-scale for evolution. Strikingly, this suggests that these viruses could have diverged at least hundreds of thousands of years ago, and hence have evolved over longer time-scales than previously suggested. We propose that the evolutionary rate and time-scale of pithovirus evolution should be reconsidered in the light of these observations and that future estimates of the rate of giant virus evolution should be carefully examined in the context of their biological plausibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ve/vey006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829572PMC
January 2018