Dataset Information

Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.

ABSTRACT: Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-more serotypes and characterised by distinct virulence gene complement and geographic range. Within the S. flexneri PGs we identify geographically restricted sub-lineages that appear to have persistently colonised regions for many decades to over 100 years. Although we found abundant evidence of antimicrobial resistance (AMR) determinant acquisition, our dataset shows no evidence of subsequent intercontinental spread of antimicrobial resistant strains. The pattern of colonisation and AMR gene acquisition suggest that S. flexneri has a distinct life-cycle involving local persistence.

SUBMITTER: Connor TR

PROVIDER: S-EPMC4522646 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.

Connor Thomas R TR Barker Clare R CR Baker Kate S KS Weill François-Xavier FX Talukder Kaisar Ali KA Smith Anthony M AM Baker Stephen S Gouali Malika M Pham Thanh Duy D Jahan Azmi Ishrat I Dias da Silveira Wanderley W Semmler Torsten T Wieler Lothar H LH Jenkins Claire C Cravioto Alejandro A Faruque Shah M SM Parkhill Julian J Wook Kim Dong D Keddy Karen H KH Thomson Nicholas R NR

eLife 20150804

Shigella flexneri is the most common cause of bacterial dysentery in low-income countries. Despite this, S. flexneri remains largely unexplored from a genomic standpoint and is still described using a vocabulary based on serotyping reactions developed over half-a-century ago. Here we combine whole genome sequencing with geographical and temporal data to examine the natural history of the species. Our analysis subdivides S. flexneri into seven phylogenetic groups (PGs); each containing two-or-mor ...[more]

PMID: 26238191

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Project description:Shigella is the second leading cause of bacterial diarrhea worldwide. Recently, Shigella sonnei seems to be replacing Shigella flexneri in low- and middle-income countries undergoing economic development. Despite this, studies focusing on these species at the genomic level remain largely unexplored. Here, we compared the genome sequences of S. flexneri and S. sonnei isolates from India with the publicly available genomes of global strains. Our analysis provides evidence for the long-term persistence of all phylogenetic groups (PGs) of S. flexneri and the recent dominance of the ciprofloxacin-resistant S. sonnei lineage in India. Within S. flexneri PGs, the majority of the study isolates belonged to PG3 within the predominance of serotype 2. For S. sonnei, the current pandemic involves globally distributed multidrug-resistant (MDR) clones that belong to Central Asia lineage III. The presence of such epidemiologically dominant lineages in association with stable antimicrobial resistance (AMR) determinants results in successful survival in the community.IMPORTANCEShigella is the second leading cause of bacterial diarrhea worldwide. This has been categorized as a priority pathogen among enteric bacteria by the Global Antimicrobial Resistance Surveillance System (GLASS) of the World Health Organization (WHO). Recently, S. sonnei seems to be replacing S. flexneri in low- and middle-income countries undergoing economic development. Antimicrobial resistance in S. flexneri and S. sonnei is a growing international concern, specifically with the international dominance of the multidrug-resistant (MDR) lineage. Genomic studies focusing on S. flexneri and S. sonnei in India remain largely unexplored. This study provides information on the introduction and expansion of drug-resistant Shigella strains in India for the first time by comparing the genome sequences of S. flexneri and S. sonnei isolates from India with the publicly available genomes of global strains. The study discusses the key differences between the two dominant species of Shigella at the genomic level to understand the evolutionary trends and genome dynamics of emerging and existing resistance clones. The present work demonstrates evidence for the long-term persistence of all PGs of S. flexneri and the recent dominance of a ciprofloxacin-resistant S. sonnei lineage in India.

Project description:For many intracellular pathogens, their virulence depends on an ability to spread between cells of an epithelial layer. For intercellular spread to occur, these pathogens deform the plasma membrane into a protrusion structure that is engulfed by the neighboring cell. Although the polymerization of actin is essential for spread, how these pathogens manipulate the actin cytoskeleton in a manner that enables protrusion formation is still incompletely understood. Here, we identify the mammalian actin binding protein synaptopodin as required for efficient intercellular spread. Using a model cytosolic pathogen, Shigella flexneri, we show that synaptopodin increases actin recruitment around bacteria and stabilizes the position of the actin tail at the posterior pole of the bacteria. We show that synaptopodin presence enables protrusions to form and to resolve at a greater rate, indicating that the proper alignment of the tail enables the bacteria to push against the membrane with greater force. We demonstrate that synaptopodin recruitment around bacteria requires the bacterial protein IcsA, and we show that this recruitment is further enhanced in a type 3 secretion system dependent manner. Myosin X, known to enhance protrusion formation, is associated with more intracellular bacteria in the presence of synaptopodin. These data establish synaptopodin as required for intracellular bacteria to reprogram the actin cytoskeleton in a manner that enables efficient protrusion formation and enhance our understanding of the cellular function of synaptopodin.SignificanceIntercellular spread is essential for many cytosolic dwelling pathogens during their infectious life cycle. Despite knowing the steps required for intercellular spread, relatively little is known about the host-pathogen interactions that enable these steps to occur. Here, we identify a requirement for the actin binding protein synaptopodin during intercellular spread by cytosolic bacteria. We show synaptopodin is necessary for the organization and abundance of actin around bacteria. We also demonstrate synaptopodin is necessary for the formation of plasma membrane structures known as protrusions that are necessary for the movement of these bacteria between cells. Thus, these findings implicate synaptopodin as an important actin-binding protein for the virulence of intracellular pathogens that require the actin cytoskeleton and spread between cells.

Dataset Information

Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.

Publications

Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri.

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