Dataset Information

Opposing roles of ?B and ?B-controlled SpoVG in the global regulation of esxA in Staphylococcus aureus.

ABSTRACT: BACKGROUND: The production of virulence factors in Staphylococcus aureus is tightly controlled by a complex web of interacting regulators. EsxA is one of the virulence factors that are excreted by the specialized, type VII-like Ess secretion system of S. aureus. The esxA gene is part of the ?B-dependent SpoVG subregulon. However, the mode of action of SpoVG and its impact on other global regulators acting on esxA transcription is as yet unknown. RESULTS: We demonstrate that the transcription of esxA is controlled by a regulatory cascade involving downstream ?B-dependent regulatory elements, including the staphylococcal accessory regulator SarA, the ArlRS two-component system and SpoVG. The esxA gene, preceding the ess gene cluster, was shown to form a monocistronic transcript that is driven by a ?A promoter, whereas a putative ?B promoter identified upstream of the ?A promoter was shown to be inactive. Transcription of esxA was strongly upregulated upon either sarA or sigB inactivation, but decreased in agr, arlR and spoVG single mutants, suggesting that agr, ArlR and SpoVG are able to increase esxA transcription and relieve the repressing effect of the ?B-controlled SarA on esxA. CONCLUSION: SpoVG is a ?B-dependent element that fine-tunes the expression of esxA by counteracting the ?B-induced repressing activity of the transcriptional regulator SarA and activates esxA transcription.

SUBMITTER: Schulthess B

PROVIDER: S-EPMC3313859 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Opposing roles of σB and σB-controlled SpoVG in the global regulation of esxA in Staphylococcus aureus.

Schulthess Bettina B Bloes Dominik A DA Berger-Bächi Brigitte B

BMC microbiology 20120124

<h4>Background</h4>The production of virulence factors in Staphylococcus aureus is tightly controlled by a complex web of interacting regulators. EsxA is one of the virulence factors that are excreted by the specialized, type VII-like Ess secretion system of S. aureus. The esxA gene is part of the σB-dependent SpoVG subregulon. However, the mode of action of SpoVG and its impact on other global regulators acting on esxA transcription is as yet unknown.<h4>Results</h4>We demonstrate that the tran ...[more]

PMID: 22272815

Similar Datasets

Project description:Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs) to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways have been shown to contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways responsible for the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, only two PRR pathways – the Toll-like receptor (TLR) and Stimulator of Interferon Gene (STING) pathways - were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated an inflammatory program, STING signaling activated an antiviral/type I interferon response, and both pathways contributed to a program linking innate and adaptive immunity. Only a small number of genes were induced in the absence of TLR or STING signaling, and these genes possessed a strong hypoxia signature. STING pathway activation required live S. aureus and was largely dependent on the DNA sensor cyclic guanosine-adenosine synthase (cGAS) recognition of S. aureus DNA. Interestingly, using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus, with TLR signaling being required for protective interleukin (IL)-1 and neutrophil recruitment and STING signaling having an opposite effect. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered byS. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus.

Dataset Information

Opposing roles of ?B and ?B-controlled SpoVG in the global regulation of esxA in Staphylococcus aureus.

Publications

Opposing roles of σB and σB-controlled SpoVG in the global regulation of esxA in Staphylococcus aureus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure