WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum

Abstract During the course of infection, pathogenic mycobacteria including Mycobacterium tuberculosis (M. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. Mycobacterial responses to changes o...

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Autores principales:	Jing Wu, Huan-wei Ru, Zhi-hao Xiang, Jun Jiang, Yu-chen Wang, Lu Zhang, Jun Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/69ae5afbba354cb48736b6883ee46632
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spelling	oai:doaj.org-article:69ae5afbba354cb48736b6883ee466322021-12-02T11:41:11ZWhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum10.1038/s41598-017-03020-42045-2322https://doaj.org/article/69ae5afbba354cb48736b6883ee466322017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03020-4https://doaj.org/toc/2045-2322Abstract During the course of infection, pathogenic mycobacteria including Mycobacterium tuberculosis (M. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. Mycobacterial responses to changes of oxygen tension are critically related to infection outcomes, such as latency and reactivation. WhiB4 is an iron-sulfur containing transcription factor that is highly sensitive to oxygen exposure. In this study, we found that WhiB4 of Mycobacterium marinum (M. marinum), a pathogenic mycobacterial species that is closely related to M. tb, is required for its virulence. M. marinum ΔwhiB4 exhibited defective intracellular replication in macrophages and diminished virulence in zebrafish. Histology analysis revealed that the host had successfully controlled ΔwhiB4 bacteria, forming well-organized granulomas. RNA-seq analysis identified a large number of pe/ppe genes that were regulated by WhiB4, which provides an explanation for the essential role of WhiB4 in M. marinum virulence. Several antioxidant enzymes were also upregulated in ΔwhiB4, supporting its role in modulation of oxidative stress response. Taken together, we have provided new insight into and proposed a model to explain the physiological role of WhiB4.Jing WuHuan-wei RuZhi-hao XiangJun JiangYu-chen WangLu ZhangJun LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Wu Huan-wei Ru Zhi-hao Xiang Jun Jiang Yu-chen Wang Lu Zhang Jun Liu WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum
description	Abstract During the course of infection, pathogenic mycobacteria including Mycobacterium tuberculosis (M. tb) encounter host environments of variable oxygen tension, ranging from the hypoxic center of granulomas to the most oxygenated region in the lung cavities. Mycobacterial responses to changes of oxygen tension are critically related to infection outcomes, such as latency and reactivation. WhiB4 is an iron-sulfur containing transcription factor that is highly sensitive to oxygen exposure. In this study, we found that WhiB4 of Mycobacterium marinum (M. marinum), a pathogenic mycobacterial species that is closely related to M. tb, is required for its virulence. M. marinum ΔwhiB4 exhibited defective intracellular replication in macrophages and diminished virulence in zebrafish. Histology analysis revealed that the host had successfully controlled ΔwhiB4 bacteria, forming well-organized granulomas. RNA-seq analysis identified a large number of pe/ppe genes that were regulated by WhiB4, which provides an explanation for the essential role of WhiB4 in M. marinum virulence. Several antioxidant enzymes were also upregulated in ΔwhiB4, supporting its role in modulation of oxidative stress response. Taken together, we have provided new insight into and proposed a model to explain the physiological role of WhiB4.
format	article
author	Jing Wu Huan-wei Ru Zhi-hao Xiang Jun Jiang Yu-chen Wang Lu Zhang Jun Liu
author_facet	Jing Wu Huan-wei Ru Zhi-hao Xiang Jun Jiang Yu-chen Wang Lu Zhang Jun Liu
author_sort	Jing Wu
title	WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum
title_short	WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum
title_full	WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum
title_fullStr	WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum
title_full_unstemmed	WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum
title_sort	whib4 regulates the pe/ppe gene family and is essential for virulence of mycobacterium marinum
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/69ae5afbba354cb48736b6883ee46632
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WhiB4 Regulates the PE/PPE Gene Family and is Essential for Virulence of Mycobacterium marinum

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