Genome-wide identification of novel genomic islands that contribute to<i>Salmonella</i>virulence in mouse systemic infection

Haneda, Takeshi; Ishii, Yuta; Danbara, Hirofumi; Okada, Nobuhiko

doi:10.1111/j.1574-6968.2009.01686.x

Cited by 50 publications

(54 citation statements)

References 42 publications

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“…2B). We obtained combined (liver and spleen) CI values for these mutants of 0.39 and 0.43, respectively (see Table S5 in the supplemental material), that were in agreement with previously reported data for deletion of the entire SPI-6 locus (19). This defect in systemic dissemination was successfully complemented by plasmid-based expression of sciG under the control of its native promoter.…”

Section: Resultssupporting

confidence: 77%

“…T6SS variants have been acquired at least three times within the Salmonella lineage, and little is known about their function and mechanism, although most reports have implicated roles for the S. Typhimurium SPI-6 T6SS in the pathogenesis of mice and infection of macrophages (5,9,17,19,24,28,30,38). We found that the disruption of noncore T6SS clusters 2 and 4 caused significant defects in systemic dissemination in mice and that disruption of noncore gene clusters 1 and 3 resulted in a significant intracellular replication defect in macrophages.…”

Section: Discussionmentioning

confidence: 99%

“…This cluster contains Rhs family genes and Rhs-associated genes that are commonly linked with T6SSs and which are extensively distributed in Gram-negative proteobacteria (55). We disrupted sciW, rhs1, and rhs2 and found that disruption of rhs2 produced the same defect in systemic dissemination in mice as disruption of core T6SS genes and the entire SPI-6 locus (19). This Rhs element is located with sciX in a bicistronic operon and may also function as a toxin/immunity gene pair participating in contact-dependent growth inhibition (40).…”

Section: Figmentioning

confidence: 99%

“…Deletion of SCI resulted in an approximately 50% reduction in internalization of HEp-2 cells that could not be complemented by PagN expression; however, complementation with safABCD or sinR was not tested (16). Disruption of SPI-6 has also been found to result in a defect in systemic dissemination in orally infected BALB/c mice (19). In support, a number of SPI-6 T6SS genes have been implicated in long-term persistence in macrophages and mice through transposon mutagenesis; however, these transposon mutations have not been verified by precise deletions (9,24,28).…”

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confidence: 99%

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Type VI Secretion System-Associated Gene Clusters Contribute to Pathogenesis of Salmonella enterica Serovar Typhimurium

2012

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ABSTRACTThe enteropathogenSalmonella entericaserovar Typhimurium employs a suite of tightly regulated virulence factors within the intracellular compartment of phagocytic host cells resulting in systemic dissemination in mice. A type VI secretion system (T6SS) withinSalmonellapathogenicity island 6 (SPI-6) has been implicated in this process; however, the regulatory inputs and the roles of noncore genes in this system are not well understood. Here we describe four clusters of noncore T6SS genes in SPI-6 based on a comparative relationship with the T6SS-3 ofBurkholderia malleiand report that the disruption of these genes results in defects in intracellular replication and systemic dissemination in mice. In addition, we show that the expression of the SPI-6-encoded Hcp and VgrG orthologs is enhanced during late stages of macrophage infection. We identify six regions that are transcriptionally active during cell infections and that have regulatory contributions from the regulators of virulence SsrB, PhoP, and SlyA. We show that levels of protein expression are very weak underin vitroconditions and that expression is not enhanced upon the deletion ofssrB,phoP,slyA,qseC,ompR, orhfq, suggesting an unknown activating factor. These data suggest that the SPI-6 T6SS has been integrated into theSalmonellaTyphimurium virulence network and customized for host-pathogen interactions through the action of noncore genes.

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Section: Resultssupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Figmentioning

confidence: 99%

mentioning

confidence: 99%

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Type VI Secretion System-Associated Gene Clusters Contribute to Pathogenesis of Salmonella enterica Serovar Typhimurium

2012

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“…STM3117 (Gene ID: 1254640) shares only 24 % homology with the Ni + -dependent glyoxalase I of Escherichia coli. Curiously, STM3117 is part of the virulence-associated operon (STM3117-3120) (Haneda et al, 2009) which has three downstream coding regions and was predicted to be involved in the methylglyoxal pathway (Shi et al, 2006). The STM3117-3120 operon along with a stretch of 14 downstream ORFs, clustered adjacent to the tRNA pheV gene, have been denoted as Salmonella pathogenicity island (SPI)-13 due to the characteristic low G+C content, similar to typical pathogenicity islands (Shah et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Salmonella methylglyoxal detoxification by STM3117-encoded lactoylglutathione lyase affects virulence in coordination with Salmonella pathogenicity island 2 and phagosomal acidification

et al. 2014

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Intracellular pathogens such as Salmonella enterica serovar Typhimurium (S. Typhimurium) manipulate their host cells through the interplay of various virulence factors. A multitude of such virulence factors are encoded on the genome of S. Typhimurium and are usually organized in pathogenicity islands. The virulence-associated genomic stretch of STM3117–3120 has structural features of pathogenicity islands and is present exclusively in non-typhoidal serovars of Salmonella. It encodes metabolic enzymes predicted to be involved in methylglyoxal metabolism. STM3117-encoded lactoylglutathione lyase significantly impacts the proliferation of intracellular Salmonella. The deletion mutant of STM3117 (Δlgl) fails to grow in epithelial cells but hyper-replicates in macrophages. This difference in proliferation outcome was the consequence of failure to detoxify methylglyoxal by Δlgl, which was also reflected in the form of oxidative DNA damage and upregulation of kefB in the mutant. Within macrophages, the toxicity of methylglyoxal adducts elicits the potassium efflux channel (KefB) in the mutant which subsequently modulates the acidification of mutant-containing vacuoles (MCVs). The perturbation in the pH of the MCV milieu and bacterial cytosol enhances the Salmonella pathogenicity island 2 translocation in Δlgl, increasing its net growth within macrophages. In epithelial cells, however, the maturation of Δlgl-containing vacuoles were affected as these non-phagocytic cells maintain less acidic vacuoles compared to those in macrophages. Remarkably, ectopic expression of Toll-like receptors 2 and 4 on epithelial cells partially restored the survival of Δlgl. This study identified a novel metabolic enzyme in S. Typhimurium whose activity during intracellular infection within a given host cell type differentially affected the virulence of the bacteria.

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The type VI secretion system gene cluster ofSalmonella typhimurium: Required for full virulence in mice

Liu

Guo

et al. 2012

J. Basic Microbiol.

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Type VI secretion system (T6SS) has increasingly been believed to participate in the infection process for many bacterial pathogens, but its role in the virulence of Salmonella typhimurium remains unclear. To look into this, we deleted the T6SS cluster from the genome of S. typhimurium 14028s and analyzed the phenotype of the resulting T6SS knockout mutant (T6SSKO mutant) in vitro and in vivo. We found that the T6SSKO mutant exhibited reduced capability in colonizing the spleen and liver in an in vivo colonization competition model in BALB/c mice infected by the oral route. Additionally, infection via intraperitoneal administration also showed that the T6SSKO mutant was less capable of colonizing the mouse spleen and liver than the wild-type strain. We did not detect significant differences between the T6SSKO and wild-type strains in epithelial cell invasion tests. However, in the macrophage RAW264.7 cell line, the T6SSKO mutant survived and proliferated significantly more poorly than the wild-type strain. These findings indicate that T6SS gene cluster is required for full virulence of S. typhimurium 14028s in BALB/c mice, possibly due to its roles in bacterial survival and proliferation in macrophages.

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Genome-wide identification of novel genomic islands that contribute toSalmonellavirulence in mouse systemic infection

Cited by 50 publications

References 42 publications

Type VI Secretion System-Associated Gene Clusters Contribute to Pathogenesis of Salmonella enterica Serovar Typhimurium

Type VI Secretion System-Associated Gene Clusters Contribute to Pathogenesis of Salmonella enterica Serovar Typhimurium

Salmonella methylglyoxal detoxification by STM3117-encoded lactoylglutathione lyase affects virulence in coordination with Salmonella pathogenicity island 2 and phagosomal acidification

The type VI secretion system gene cluster ofSalmonella typhimurium: Required for full virulence in mice

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