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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Danio rerio Mycobacterium marinum

PROVIDER: GSE178191 | GEO | 2021/06/16

REPOSITORIES: GEO

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WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [zebrafish RNAseq]

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.

2021-06-16 | GSE178186 | GEO

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

2021-11-22 | GSE189123 | GEO

WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [ChIP-Seq]

2021-06-16 | GSE178190 | GEO

WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [bacteria RNA seq]

2021-06-16 | GSE178188 | GEO

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

Project description:WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish

| PRJNA737631 | ENA

WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [zebrafish RNAseq]

Project description:WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [zebrafish RNAseq]

| PRJNA737628 | ENA

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

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

| PRJNA781600 | ENA

WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [ChIP-Seq]

Project description:WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [ChIP-Seq]

| PRJNA737635 | ENA

WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [bacteria RNA seq]

Project description:WhiB4 is required for the reactivation of latent infection of Mycobacterium marinum in zebrafish [bacteria RNA seq]

| PRJNA737634 | ENA

Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.

Project description:The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (≈ 35 bacteria) of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%), stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5-10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive.

| S-EPMC3459992 | biostudies-literature

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