Mycobacterial WhiB6 Differentially Regulates ESX-1 and the Dos Regulon to Modulate Granuloma Formation and Virulence in Zebrafish

Autor: Zhenkang Chen, Yangbo Hu, Bridgette M. Cumming, Pei Lu, Lipeng Feng, Jiaoyu Deng, Adrie J.C. Steyn, Shiyun Chen
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Cell Reports, Vol 16, Iss 9, Pp 2512-2524 (2016)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2016.07.080
Popis: During the course of infection, Mycobacterium tuberculosis (Mtb) is exposed to diverse redox stresses that trigger metabolic and physiological changes. How these stressors are sensed and relayed to the Mtb transcriptional apparatus remains unclear. Here, we provide evidence that WhiB6 differentially regulates the ESX-1 and DosR regulons through its Fe-S cluster. When challenged with NO, WhiB6 continually activates expression of the DosR regulons but regulates ESX-1 expression through initial activation followed by gradual inhibition. Comparative transcriptomic analysis of the holo- and reduced apo-WhiB6 complemented strains confirms these results and also reveals that WhiB6 controls aerobic and anaerobic metabolism, cell division, and virulence. Using the Mycobacterium marinum zebrafish infection model, we find that holo- and apo-WhiB6 modulate levels of mycobacterial infection, granuloma formation, and dissemination. These findings provide fresh insight into the role of WhiB6 in mycobacterial infection, dissemination, and disease development.
Databáze: Directory of Open Access Journals