Dataset Information

Mapping and regulation of genes within Salmonella pathogenicity island 12 that contribute to in vivo fitness of Salmonella enterica Serovar Typhimurium.

ABSTRACT: Salmonella pathogenicity island 12 (SPI-12) of Salmonella enterica serovar Typhimurium is a 15-kb region that encompasses genes STM2230 to STM2245 and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for four genes in SPI-12 for bacterial survival in the host. STM2239, a potential Q antiterminator, showed a prominent contribution to bacterial fitness. Transcriptional reporter experiments, quantitative reverse transcription-PCR (RT-PCR), and immunoblotting demonstrated that the virulence regulator SsrB and STM2239 contribute to transcriptional activation of genes in SPI-12. SsrB was found to indirectly regulate this locus by transcriptional read-through from the sspH2 (STM2241) promoter. Chromatin immunoprecipitation showed that STM2239 copurified with the promoter regulating STM2237, suggesting that STM2239 may function as an antiterminator to activate adjacent genes. These results demonstrate that bacteriophage genes may be adapted by pathogenic bacteria to improve fitness in the host.

SUBMITTER: Tomljenovic-Berube AM

PROVIDER: S-EPMC3697593 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Mapping and regulation of genes within Salmonella pathogenicity island 12 that contribute to in vivo fitness of Salmonella enterica Serovar Typhimurium.

Tomljenovic-Berube Ana M AM Henriksbo Brandyn B Porwollik Steffen S Cooper Colin A CA Tuinema Brian R BR McClelland Michael M Coombes Brian K BK

Infection and immunity 20130429 7

Salmonella pathogenicity island 12 (SPI-12) of Salmonella enterica serovar Typhimurium is a 15-kb region that encompasses genes STM2230 to STM2245 and encodes a remnant phage known to contribute to bacterial virulence. In mouse infection experiments and replication assays in macrophages, we demonstrated a role for four genes in SPI-12 for bacterial survival in the host. STM2239, a potential Q antiterminator, showed a prominent contribution to bacterial fitness. Transcriptional reporter experimen ...[more]

PMID: 23630960

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Project description:Since 2014, Salmonella 4,[5],12:i:- has emerged as the most common serovar of Salmonella enterica identified from swine samples submitted to veterinary diagnostic laboratories in the United States. To compare the pathogenicity of S. 4,[5],12:i:- in swine to the known pathogenic Salmonella Typhimurium and lesser pathogenic Salmonella Derby, 72 pigs (20 per Salmonella serovar treatment and 12 controls) were inoculated with either S. Typhimurium, S. 4,[5],12:i:-, S. Derby, or sham-inoculated and followed for up to 28 days thereafter via rectal temperature, fecal scoring, and fecal culture. Animals were euthanized on days 2, 4, or 28 to determine the gross and histopathologic signs of disease and tissue colonization. The results clearly demonstrate that for the isolates selected, serovar 4,[5],12:i:- possesses similar ability as serovar Typhimurium to cause clinical disease, colonize the tonsils and ileocecal lymph nodes, and be shed in the feces of infected swine past resolution of clinical disease. To compare the competitive fitness of S. 4,[5],12:i:- to S. Typhimurium in swine when co-infected, 12 pigs were co-inoculated with equal concentrations of both S. Typhimurium and S. 4,[5],12:i and followed for up to 10 days thereafter. When co-inoculated, serovar 4,[5],12:i:- was consistently detected in the feces of a higher percentage of pigs and at higher concentrations than serovar Typhimurium, suggesting an increased competitive fitness of 4,[5],12:i:- relative to serovar Typhimurium when inoculated simultaneously into naïve pigs. Whole genome sequencing analysis of the isolates used in these studies revealed similar virulence factor presence in all S. 4,[5],12:i:- and S. Typhimurium isolates, but not S. Derby, providing additional evidence for similar pathogenicity potential between serovars 4,[5],12:i:- and Typhimurium. Altogether, this data strongly supports the hypothesis that S. 4,[5],12:i:- is a pathogen of swine and suggests a mechanism through increased competitive fitness for the increasing identification of Salmonella 4,[5],12:i:- in swine diagnostic samples over the past several years.

Project description:UnlabelledSalmonella enterica pathogenicity island 1 (SPI-1) encodes proteins required for invasion of gut epithelial cells. The timing of invasion is tightly controlled by a complex regulatory network. The transcription factor (TF) HilD is the master regulator of this process and senses environmental signals associated with invasion. HilD activates transcription of genes within and outside SPI-1, including six other TFs. Thus, the transcriptional program associated with host cell invasion is controlled by at least 7 TFs. However, very few of the regulatory targets are known for these TFs, and the extent of the regulatory network is unclear. In this study, we used complementary genomic approaches to map the direct regulatory targets of all 7 TFs. Our data reveal a highly complex and interconnected network that includes many previously undescribed regulatory targets. Moreover, the network extends well beyond the 7 TFs, due to the inclusion of many additional TFs and noncoding RNAs. By comparing gene expression profiles of regulatory targets for the 7 TFs, we identified many uncharacterized genes that are likely to play direct roles in invasion. We also uncovered cross talk between SPI-1 regulation and other regulatory pathways, which, in turn, identified gene clusters that likely share related functions. Our data are freely available through an intuitive online browser and represent a valuable resource for the bacterial research community.ImportanceInvasion of epithelial cells is an early step during infection by Salmonella enterica and requires secretion of specific proteins into host cells via a type III secretion system (T3SS). Most T3SS-associated proteins required for invasion are encoded in a horizontally acquired genomic locus known as Salmonella pathogenicity island 1 (SPI-1). Multiple regulators respond to environmental signals to ensure appropriate timing of SPI-1 gene expression. In particular, there are seven transcription regulators that are known to be involved in coordinating expression of SPI-1 genes. We have used complementary genome-scale approaches to map the gene targets of these seven regulators. Our data reveal a highly complex and interconnected regulatory network that includes many previously undescribed target genes. Moreover, our data functionally implicate many uncharacterized genes in the invasion process and reveal cross talk between SPI-1 regulation and other regulatory pathways. All datasets are freely available through an intuitive online browser.

Dataset Information

Mapping and regulation of genes within Salmonella pathogenicity island 12 that contribute to in vivo fitness of Salmonella enterica Serovar Typhimurium.

Publications

Mapping and regulation of genes within Salmonella pathogenicity island 12 that contribute to in vivo fitness of Salmonella enterica Serovar Typhimurium.

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