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Molecular Connectivity between Extracytoplasmic Sigma Factors and PhoP Accounts for Coupled Mycobacterial Stress Response

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Molecular Connectivity between Extracytoplasmic Sigma Factors and PhoP Accounts for Coupled Mycobacterial Stress Response
 
Creator Goar, Harsh
Paul , Partha
Khan, Hina
Sarkar, Dibyendu
 
Subject QR Microbiology
 
Description Mycobacterium tuberculosis encounters numerous stress conditions within the host, but how it is able to mount a coupled stress response remains unknown. Growing evidence suggests that under acidic pH, M. tuberculosis modulates redox homeostasis. In an attempt to dissect the mechanistic details of responses to multiple stress conditions, here we studied the significance of connectivity of extracytoplasmic sigma factors with PhoP. We show that PhoP impacts the mycothiol redox state, and the H37Rv ΔphoP deletion mutant strain displays a significantly higher susceptibility to redox stress than the wild-type bacilli. To probe how the two regulators PhoP and redox-active sigma factor SigH contribute to redox homeostasis, we show that SigH controls expression of redox-active thioredoxin genes, a major mycobacterial antioxidant system, and under redox stress, SigH, but not PhoP, is recruited at the target promoters. Consistent with these results, interaction between PhoP and SigH fails to impact redox-dependent gene expression. This is in striking contrast to our previous results showing PhoP-dependent SigE recruitment within acid-inducible mycobacterial promoters to maintain pH homeostasis. Our subsequent results demonstrate reduced PhoP-SigH interaction in the presence of diamide and enhanced PhoP-SigE interaction under low pH. These contrasting results uncover the underlying mechanism of the mycobacterial adaptive program, coupling low pH with maintenance of redox homeostasis.
 
Publisher ASM
 
Date 2022-06-21
 
Type Article
PeerReviewed
 
Relation https://journals.asm.org/doi/10.1128/jb.00110-22?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://crdd.osdd.net/open/2975/
 
Identifier Goar, Harsh and Paul , Partha and Khan, Hina and Sarkar, Dibyendu (2022) Molecular Connectivity between Extracytoplasmic Sigma Factors and PhoP Accounts for Coupled Mycobacterial Stress Response. Journal of bacteriology, 204 (06). ISSN 1098-5530