Biology subjects

Stephen Baker

Publications and source records attributed to Stephen Baker.

6 recordsLinked to original sources

bioRxiv2016

Whole genome sequence analysis of Salmonella Typhi isolated in Thailand before and after the introduction of a national immunization program

Vaccines against Salmonella Typhi, the causative agent of typhoid fever, are commonly used by travellers, however, there are few examples of national immunization programs in endemic areas. There is therefore a paucity of data on the impact of typhoid immunization programs on localised populations of S. Typhi. Here we have used whole genome sequencing (WGS) to characterise 44 historical bacterial isolates collected before and after a national typhoid immunization program that was implemented in Thailand in 1977 in response to a large outbreak; the program was highly effective in reducing typhoid case numbers. Thai isolates were highly diverse, including 10 distinct phylogenetic lineages or genotypes. Novel prophage and plasmids were also detected, including examples that were previously only reported in Shigella sonnei and Escherichia coli. The majority of S. Typhi genotypes observed prior to the immunization program were not observed following it. Post-vaccine era isolates were more closely related to S. Typhi isolated from neighbouring countries than to earlier Thai isolates, providing no evidence for the local persistence of endemic S. Typhi following the national immunization program. Rather, later cases of typhoid appeared to be caused by the occasional importation of common genotypes from neighbouring Vietnam, Laos, and Cambodia. These data show the value of WGS in understanding the impacts of vaccination on pathogen populations and provide support for the proposal that large-scale typhoid immunization programs in endemic areas could result in lasting local disease elimination, although larger prospective studies are needed to test this directly.\n\nAuthor SummaryTyphoid fever is a systemic infection caused by the bacterium Salmonella Typhi. Typhoid fever is associated with inadequate hygiene in low-income settings and a lack of sanitation infrastructure. A sustained outbreak of typhoid fever occurred in Thailand in the 1970s, which peaked in 1975-1976. In response to this typhoid fever outbreak the government of Thailand initiated an immunization program, which resulted in a dramatic reduction in the number of typhoid cases in Thailand. To better understand the population of S. Typhi circulating in Thailand at this time, as well as the impact of the immunization program on the pathogen population, we sequenced the genomes of 44 S. Typhi obtained from hospitals in Thailand before and after the immunization program. The genome sequences showed that isolates of S. Typhi bacteria isolated from post-immunization era typhoid cases were likely imported from neighbouring countries, rather than strains that have persisted in Thailand throughout the immunization period. Our work provides the first historical insights into S. Typhi in Thailand during the 1970s, and provides a model for the impact of immunization on S. Typhi populations.

Genomics↗

bioRxiv2016

Unbiased whole-genome deep sequencing of human and porcine stool samples reveals circulation of multiple groups of rotaviruses and a putative zoonotic infection

Coordinated and synchronous virological surveillance for zoonotic viruses in both human clinical cases and animal reservoirs provides an opportunity to identify interspecies virus movement. Rotavirus is an important cause of viral gastroenteritis in humans and animals. We have documented the rotavirus diversity within co-located humans and animals sampled from the Mekong delta region of Vietnam using a primer-independent, agnostic, deep sequencing approach. A total of 296 stool samples (146 from diarrhoeal human patients and 150 from pigs living in the same geographical region) were directly sequenced, generating the genomic sequences of 60 human rotaviruses (all group A) and 31 porcine rotaviruses (13 group A, 7 group B, 6 group C and 5 group H). Phylogenetic analyses showed the co-circulation of multiple distinct rotavirus group A (RVA) genotypes/strains, many of which were divergent from the strain components of licensed RVA vaccines, as well as considerable virus diversity in pigs including full genomes of rotaviruses in groups B, C and H, none of which have been previously reported in Vietnam. Furthermore the detection of an atypical RVA genotype constellation (G4-P[6]-I1-R1-C1-M1-A8-N1-T7-E1-H1) in a human patient and a pig from the same region provides some evidence for a zoonotic event

Genomics↗

bioRxiv2016

Whole genome sequencing identifies independent outbreaks of Shigellosis in 2010 and 2011 in La Pampa Province, Argentina

Shigella sonnei is an emergent cause of diarrheal disease in middle-income countries. The organism causes endemic disease and is also associated with sporadic outbreaks in susceptible populations. In 2010 and 2011 there were two suspected outbreaks of diarrheal disease caused by S. sonnei in La Pampa province in central Argentina. Aiming to confirm these as outbreaks and provide insight into the relationship of the strains causing these infections we combined antimicrobial susceptibility testing and pulsed field gel electrophoresis (PFGE) with whole genome sequencing (WGS). Antimicrobial susceptibility testing suggested the two events were unrelated; organisms isolated in 2010 exhibited resistance to trimethoprim sulphate whereas the 2011 S. sonnei were non-susceptible against ampicillin, trimethoprim sulphate and cefpodoxime. PFGE profiling confirmed the likelihood of two independent outbreaks, separating the isolates into two main XbaI restriction profiles. We additionally performed WGS on 17 isolates associated with these outbreaks. The resulting phylogeny confirmed the PFGE structure and separated the organisms into two comparatively distantly related clones. Antimicrobial resistant genes were common, and the presence of an OXA-1 was likely associated with resistance to cefpodoxime in the second outbreak. We additionally identified novel horizontally transferred genetic material that may impinge on the pathogenic phenotype of the infecting strains. Our study shows that even with a lack of supporting routine data WGS is an indispensible method for the tracking and surveillance of bacterial pathogens during outbreaks and is becoming a vital tool for the monitoring of antimicrobial resistant strains of S. sonnei.

Genomics↗

bioRxiv2016

South Asia as a reservoir for the global spread of ciprofloxacin resistant Shigella sonnei

BackgroundAntimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin resistant S. sonnei are being increasingly isolated in Asia, and sporadically reported on other continents.\n\nMethods and FindingsHypothesising that Asia is the hub for the recent international spread of ciprofloxacin resistant S. sonnei, we performed whole genome sequencing on a collection of contemporaneous ciprofloxacin resistant S. sonnei isolated in six countries from within and outside of Asia. We reconstructed the recent evolutionary history of these organisms and combined these data with their geographical location of isolation. Placing these sequences into a global phylogeny we found that all ciprofloxacin resistant S. sonnei formed a single clade within a Central Asian expansion of Lineage III. Further, our data show that resistance to ciprofloxacin within S. sonnei can be globally attributed to a single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I and gyrA-D87G mutations. Geographical data predict that South Asia is the likely primary source of these organisms, which are being regularly exported across Asia and intercontinentally into Australia, the USA and Europe.\n\nConclusionsThis study shows that a single clone, which is widespread in South Asia, is driving the current intercontinental surge of ciprofloxacin resistant S. sonnei and is capable of establishing endemic transmission in new locations. Despite being limited in geographical scope, our work has major implications for understanding the international transfer of antimicrobial resistant S. sonnei, and provides a tractable model for studying how antimicrobial resistant Gram-negative community acquired pathogens spread globally.

Microbiology↗

bioRxiv2016

Inducible colistin resistance via a disrupted plasmid-borne mcr-1 gene in a 2008 Vietnamese Shigella sonnei isolate

The mcr-1 gene, which confers resistance against the last-resort antimicrobial colistin, was recently discovered in Enterobacteriaceae circulating in China. Through genome sequencing we identified a plasmid-associated inactive form of mcr-1 in a 2008 Vietnamese isolate of Shigella sonnei. The plasmid was conjugated into E. coli and mcr-1 was activated upon exposure to colistin, suggesting the gene has been circulating in human-restricted pathogens for some time but carries a selective fitness cost.

Microbiology↗

bioRxiv2014

Extensive capsule locus variation and large-scale genomic recombination within the Klebsiella pneumoniae clonal complex 258/11.

Klebsiella pneumoniae clonal complex (CC) 258/11, comprising sequence types (STs) 258, 11 and closely related STs, is associated with dissemination of the K. pneumoniae carbapenemase (KPC). Hospital outbreaks of KPC CC258/11 infections have been observed globally and are very difficult to treat. As a consequence there is renewed interest in alternative infection control measures such as vaccines and phage or depolymerase treatments targeting the K pneumoniae polysaccharide capsule. To date, 78 immunologically distinct capsule variants have been described in K. pneumoniae. Previous investigations of ST258 and a small number of closely related strains suggested capsular variation was limited within this clone; only two distinct ST258 capsular synthesis (cps) loci have been identified, both acquired through large-scale recombination events (>50 kbp). Here we report comparative genomic analysis of the broader K. pneumoniae CC258/11. Our data indicate that several large-scale recombination events have shaped the genomes of CC258/11, and that definition of the complex should be broadened to include ST395 (also reported to harbour KPC). We identified 11 different cps loci within CC258/11, suggesting that capsular switching is actually common within the complex. We also observed several insertion sequences (IS) within the cps loci, and show further diversification of two loci through IS activity. These findings suggest the capsular loci of clinically important K. pneumoniae are under diversifying selection, which alters our understanding of the evolution of this important clone and has implications for the design of control measures targeting the capsule.

Genomics↗