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Mycobacterium marinum ATCC BAA-535

ABSTRACT: WhiB6 Differentially Regulates ESX-1 and Dos Regulon to Modulate Transition between Resuscitation and Dormancy during Mycobacterial Infection

PROVIDER: PRJNA318836 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3439791.fastq.gz	Fastqsanger.gz
	SRR3439785.fastq.gz	Fastqsanger.gz
	SRR3439786.fastq.gz	Fastqsanger.gz
	SRR3439787.fastq.gz	Fastqsanger.gz
	SRR3439788.fastq.gz	Fastqsanger.gz

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

Project description: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.

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Mycobacterium marinum ATCC BAA-535

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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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Mycobacterium marinum

Project description: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

Project description:Tuberculosis is an infectious disease, with latent infection with Mycobacterium tuberculosis (M.tb) affecting 1/3 of humanity. It can remain quiescent for long time, making eradication very difficult. To do so, M.tb need to carefully orchestrate its gene expression to survive immune response and starvation but still be able to reactivate to enable transmission to new hosts. Here we used whole transcriptome deep sequencing to compare gene expression between wild type M.tb and a strain with its whiB6, a gene encoding a putative redox-sensing transcription factor, disrupted by a transposon. We found several genes associated with dormancy such as hspX, fdxA and narK2 upregulated in the transposon mutant, indicating that WhiB6 may be a repressor of such genes. The results suggest that WhiB6 may be a complement to the dosS/dosR system in regulating genes important for dormancy. Triplicate cultures of a mutant with its whiB6 gene disrupted by a transposon and wild-type M. tuberculosis CDC1551 were grown in 7H9 media. RNA was extracted and depleted from rRNA. Global gene expression was measured using AB SOLID RNA sequencing.

2013-09-18 | E-GEOD-40941 | biostudies-arrayexpress

Transcriptional profile of Mycobacterium tuberculosis espL deletion mutant

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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Transcription profiling by tiling array of Potassium availability triggers Mycobacterium tuberculosis transition to, and resuscitation from, non-culturable (dormant) states

Project description:Dormancy in non-sporulating bacteria is an interesting and underexplored phenomenon with significant medical implications. In particular, latent tuberculosis may result from the maintenance of Mycobacterium tuberculosis bacilli in non-replicating states in infected individuals. Uniquely, growth of M. tuberculosis in aerobic conditions in potassium-deficient media resulted in the generation of bacilli that were non-culturable (NC) on solid media but detectable in liquid media. These bacilli were morphologically distinct and tolerant to cell-wall-targeting antimicrobials. Bacterial counts on solid media quickly recovered after washing and incubating bacilli in fresh resuscitation media containing potassium. This resuscitation of growth occurred too quickly to be attributed to M. tuberculosis replication. Transcriptomic and proteomic profiling through adaptation to, and resuscitation from, this NC state revealed a switch to anaerobic respiration and a shift to lipid and amino acid metabolism. High concordance with mRNA signatures derived from M. tuberculosis infection models suggests that analogous NC mycobacterial phenotypes may exist during disease and may represent unrecognized populations in vivo. Resuscitation of NC bacilli in potassium-sufficient media was characterized by time-dependent activation of metabolic pathways in a programmed series of processes that probably transit bacilli through challenging microenvironments during infection. [Data is also available from http://bugs.sgul.ac.uk/E-BUGS-151]

2015-02-25 | E-BUGS-151 | biostudies-arrayexpress

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WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish II

Project description:Granulomas are the pathological hallmark of tuberculosis (TB). In individuals latently infected with Mycobacterium tuberculosis (M. tb), the bacteria are thought to reside within the granulomas in a nonreplicating dormant state due to the lack of oxygen and nutrients. However, a portion of these individuals will develop active TB and little is known on the bacterial mechanisms/factors involved in this process. In this study, we found that WhiB4, an oxygen sensor and a transcription factor, plays a critical role in disease progression and reactivation of Mycobacterium marinum (M. marinum) infection in zebrafish. We show that the whiB4 mutant of M. marinum caused latent infection in adult zebrafish, which is characterized by the stable bacterial loads, constant number of non-necrotized granulomas in fewer organs, and reduced immune responses compared to zebrafish infected with the wild type bacteria or the complemented strain. The mutant bacteria in zebrafish were also less responsive to antibiotic treatments. Moreover, the whiB4 mutant was defective in resuscitation from hypoxia-induced dormancy and that the DosR regulon was dysregulated in the mutant. Taken together, our results suggest that WhiB4 is a major driver of reactivation from latent infection and that WhiB4 is an attractive target for the development of novel therapeutics, which may help to prevent the reactivation of latent infection thereby reducing the incidences of active TB.

2021-11-22 | GSE189123 | GEO

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