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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 Mycobacterium marinum.

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