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

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

PROVIDER: PRJNA511673 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8368680_1.fastq.gz	Fastqsanger.gz
	SRR8368680_2.fastq.gz	Fastqsanger.gz
	SRR8368690_1.fastq.gz	Fastqsanger.gz
	SRR8368690_2.fastq.gz	Fastqsanger.gz
	SRR8368671_1.fastq.gz	Fastqsanger.gz

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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.

2018-12-25 | GSE124341 | GEO

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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Proteolytic-independent role of mycosins in stabilization of the ESX-1 and ESX-5 type VII secretion membrane complexes.

Project description:Pathogenic mycobacteria contain up to five type VII secretion (T7S) systems, ESX-1 to ESX-5, which have central roles in virulence and viability. One of the conserved components of these systems, the serine protease mycosin (MycP), has been shown to be essential for secretion by ESX-1 and ESX-5. However, here we show that protease activity of MycP1 and MycP5 of M. marinum is not essential for ESX-1 and ESX-5 dependent secretion, respectively. This indicates that MycP has a second, so far unknown, function that is essential for T7S. To investigate whether this second role is related to proper functioning of the T7S membrane core complex, we first verified that the ESX-1 membrane complex is of similar composition and size as the previously analyzed ESX-5 complex and that MycP1 and MycP5 are not an integral part of the respective core complex. In contrast, we could not detect ESX-1 and ESX-5 complexes under mycP1 and mycP5 knockout conditions, respectively. Interestingly, the ESX-5 complex could be detected at wild-type levels in the absence of MycP5, when membranes were subjected to crosslinking before detergent solubilization, suggesting that MycP is involved in complex stabilization. Based on our findings we hypothesize that mycosins loosely associate with their respective membrane complex, which is crucial for the full integrity and functioning of the secretion machinery.

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Gene expression profile of M.tuberculosis espR (Rv3849) mutant

Project description:Mycobacterium tuberculosis, a pathogen of global importance, utilizes the ESX-1 protein secretion system to export virulence factors that disarm host macrophages. Although this secretory pathway is critical for virulence, how ESX-1 is regulated is completely unknown. Here we show that EspR (Rv3849) is a key regulator of ESX-1. EspR activates transcription of an operon that includes three ESX-1 components, Rv3616c-Rv3614c, whose expression in turn promotes secretion of ESX-1 substrates. Keywords: Strain comparison

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Gene expression profile of M.tuberculosis espR (Rv3849) mutant complemented with an N-terminal Flag espR gene

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Global transcriptomic investigation of the human macrophage response towards pathogenic/non-pathogenic mycobacteria

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Gene expression profile of M.tuberculosis espR (Rv3849) mutant

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