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WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum

ABSTRACT: WhiB6 is a transcription factor that regulates expression of genes encoding ESX-1 substrates. We found that in the absence of the genes encoding conserved membrane components of the ESX-1 system, the expression of the whiB6 gene and genes encoding ESX-1 substrates were reduced.

ORGANISM(S): Mycobacterium marinum

PROVIDER: GSE99632 | GEO | 2017/11/27

SECONDARY ACCESSION(S): PRJNA389110

REPOSITORIES: GEO

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WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria

Project description:These data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

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WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in <i>Mycobacterium marinum</i>.

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WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria

Project description:WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria

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Characterization of ESX-1 components EccA1, EspG1 and EspH reveal pivotal role of Esp substrates in the Mycobacterium marinum infection cycle

Project description:The pathogen Mycobacterium tuberculosis employs a range of ESX-1 substrates to manipulate the host and build a successful infection. Although the importance of ESX-1 secretion in virulence is well established, the characterization of its individual components and the role of individual substrates is far from complete. Here, we describe the functional characterization of the accessory ESX-1 proteins EccA1, EspG1 and EspH, i.e. proteins that are not present in all five ESX system of mycobacteria. Proteomic analysis revealed that EspG1 is crucial for ESX-1 secretion, since all detectable ESX-1 substrates were absent from the cell surface and culture supernatant in an espG1 mutant. Deletion of eccA1 resulted in minor secretion defects, but interestingly, the severity of these secretion defects was dependent on the culture conditions. Finally, espH deletion showed a partial secretion defect, only secretion of EspE, EspF and EsxA/EsxB was blocked.

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Transcriptome analysis of M.tuberculosis using RNA-seq indicates WhiB6 repression of dormancy associated genes

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Project description:The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis. The ESX-1 cluster comprises approximately twenty genes and encodes a specialized secretion apparatus, which releases effectors into the extracellular milieu. The goal of this study is to understand the role of EspL. We show that EspL, a protein of 115 amino acids, is essential for mediating ESX-1-dependent virulence and for stabilization of EspE, EspF and EspH protein levels. Indeed, an espL knock-out mutant was unable to replicate intracellularly, secrete ESX-1 substrates or stimulate innate cytokine production. Moreover, loss of EspL also leads to downregulation in M. tuberculosis of WhiB6, a redox-sensitive transcriptional activator of ESX-1 genes.

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Transcriptome analysis of M.tuberculosis using RNA-seq indicates WhiB6 repression of dormancy associated genes

2013-09-18 | GSE40941 | GEO

Mycobacterium marinum

Project description:WhiB6 regulation of ESX-1 gene expression is controlled by a negative feedback loop in Mycobacterium marinum

| PRJNA389110 | ENA

espL deletion mutant of Mycobacterium tuberculosis

Project description:The ESX-1, type VII, secretion system represents the major virulence determinant of Mycobacterium tuberculosis, one of the most successful intracellular pathogens. Here, by combining genetic and high-throughput approaches, we show that EspL, a protein of 115 amino acids, is essential for mediating ESX-1-dependent virulence and for stabilization of EspE, EspF and EspH protein levels. Indeed, an espL knock-out mutant was unable to replicate intracellularly, secrete ESX-1 substrates or stimulate innate cytokine production. Moreover, proteomic studies detected greatly reduced amounts of EspE, EspF and EspH in the espL mutant as compared to the wild type strain, suggesting a role for EspL as a chaperone. The latter conclusion was further supported by discovering that EspL interacts with EspD, which was previously demonstrated to stabilize the ESX-1 substrates and effector proteins, EspA and EspC. Moreover, loss of EspL also leads to downregulation in M. tuberculosis of WhiB6, a redox-sensitive transcriptional activator of ESX-1 genes. Overall, our data highlight the importance of a so-far overlooked, though conserved, component of the ESX-1 secretion system and begin to delineate the role played by EspE, EspF and EspH in virulence and host-pathogen interaction.

2018-12-10 | PXD010929 | Pride

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