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      Differential gene expression profile of Shigella dysenteriae causing bacteremia in an immunocompromised individual

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          Abstract

          Aim:

          Shigella species has varying levels of virulence gene expression with respect to different sites of infection. In this study, the differential gene expression of S. dysenteriae in response to its site of infection was analyzed by transcriptomics.

          Methods:

          This study includes four clinical Shigella isolates. Transcriptomics was done for the stool and blood samples of a single patient. Isolates were screened for the presence of antimicrobial resistance genes.

          Results:

          The majority of genes involved in invasion were highly expressed in the strain isolated from the primary site of infection. Additionally, antimicrobial resistance ( dhfr1A, sulII, bla OXA. bla CTX-M-1 and qnrS) genes were identified.

          Conclusion:

          This study provides a concise view of the transcriptional expression of clinical strains and provides a basis for future functional studies on Shigella spp.

          Lay abstract

          Shigella infection is restricted to the gastrointestinal tract and rarely causes fatal extra-intestinal complications like bacteremia. There are limited studies available from India on molecular characterization of Shigella spp. In this study, we characterized four Shigella isolates obtained from bloodstream infections. Shigella spp. isolated from the stool and blood of one representative patient was further sequenced to study the differential gene expression profile. The differential protein expression by S. dysenteriae observed in this study demonstrates that it has a specific response to particular intracellular environments. Further, the in vivo mechanism of Shigellae invasion are difficult to fully study until the intracellular environment is mimicked in vitro. To the best of our knowledge, this is the first Indian study that compared the gene expression profile of clinical Shigella strains.

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          Most cited references 30

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          How bacterial pathogens colonize their hosts and invade deeper tissues.

          Bacterial pathogens have evolved a wide range of strategies to colonize and invade human organs, despite the presence of multiple host defense mechanisms. In this review, we will describe how pathogenic bacteria can adhere and multiply at the surface of host cells, how some bacteria can enter and proliferate inside these cells, and finally how pathogens may cross epithelial or endothelial host barriers and get access to internal tissues, leading to severe diseases in humans.
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            Genome dynamics and diversity of Shigella species, the etiologic agents of bacillary dysentery

            The Shigella bacteria cause bacillary dysentery, which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four representative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved primary virulence determinants. The Shigella chromosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300∼700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with variable epidemiological and pathological features.
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              The Rising Dominance of Shigella sonnei: An Intercontinental Shift in the Etiology of Bacillary Dysentery

              Shigellosis is the major global cause of dysentery. Shigella sonnei, which has historically been more commonly isolated in developed countries, is undergoing an unprecedented expansion across industrializing regions in Asia, Latin America, and the Middle East. The precise reasons underpinning the epidemiological distribution of the various Shigella species and this global surge in S. sonnei are unclear but may be due to three major environmental pressures. First, natural passive immunization with the bacterium Plesiomonas shigelloides is hypothesized to protect populations with poor water supplies against S. sonnei. Improving the quality of drinking water supplies would, therefore, result in a reduction in P. shigelloides exposure and a subsequent reduction in environmental immunization against S. sonnei. Secondly, the ubiquitous amoeba species Acanthamoeba castellanii has been shown to phagocytize S. sonnei efficiently and symbiotically, thus allowing the bacteria access to a protected niche in which to withstand chlorination and other harsh environmental conditions in temperate countries. Finally, S. sonnei has emerged from Europe and begun to spread globally only relatively recently. A strong selective pressure from localized antimicrobial use additionally appears to have had a dramatic impact on the evolution of the S. sonnei population. We hypothesize that S. sonnei, which exhibits an exceptional ability to acquire antimicrobial resistance genes from commensal and pathogenic bacteria, has a competitive advantage over S. flexneri, particularly in areas with poorly regulated antimicrobial use. Continuing improvement in the quality of global drinking water supplies alongside the rapid development of antimicrobial resistance predicts the burden and international distribution of S. sonnei will only continue to grow. An effective vaccine against S. sonnei is overdue and may become one of our only weapons against this increasingly dominant and problematic gastrointestinal pathogen.
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                Author and article information

                Journal
                Future Sci OA
                Future Sci OA
                FSOA
                Future Science OA
                Future Science Ltd (London, UK )
                2056-5623
                29 January 2020
                April 2020
                29 January 2020
                : 6
                : 4
                Affiliations
                [1 ]Department of Clinical Microbiology, Christian Medical College, Vellore 632004, India
                Author notes
                [* ]Author for correspondence: Tel.: +91 944 221 0555; vbalaji@ 123456cmcvellore.ac.in
                10.2144/fsoa-2019-0117
                7117556
                © 2020 Balaji Veeraraghavan

                This work is licensed under the Creative Commons Attribution 4.0 License

                Counts
                Pages: 9
                Product
                Categories
                Short Communication

                shigella, gene expression, rna-seq analysis, invasive, icsa

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