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Mycobacterium tuberculosis PhoP integrates stress response to intracellular survival by regulating cAMP level

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Mycobacterium tuberculosis PhoP integrates stress response to intracellular survival by regulating cAMP level
 
Creator Khan, Hina
Paul, Partha
Goar, Harsh
Bamniya, Bhanwar
Baid, Navin
Sarkar, Dibyendu
 
Subject QR Microbiology
 
Description Survival of M. tuberculosis within the host macrophages requires the bacterial virulence regulator PhoP, but the underlying reason remains unknown. cAMP is one of the most widely used second messengers, which impacts on a wide range of cellular responses in microbial pathogens including M. tuberculosis. Herein, we hypothesized that intra-bacterial cAMP level could be controlled by PhoP since this major regulator plays a key role in bacterial responses against numerous stress conditions. A transcriptomic analysis reveals that PhoP functions as a repressor of cAMP-specific phosphodiesterase (PDE) Rv0805, which hydrolyses cAMP. In keeping with these results, we find specific recruitment of the regulator within the promoter region of rv0805 PDE, and absence of phoP or ectopic expression of rv0805 independently accounts for elevated PDE synthesis leading to depletion of intra-bacterial cAMP level. Thus, genetic manipulation to inactivate PhoP-rv0805-cAMP pathway decreases cAMP level, stress tolerance and intracellular survival of the bacillus.
 
Publisher MICROBIOLOGY AND INFECTIOUS DISEASE
 
Date 2024-05
 
Type Article
PeerReviewed
 
Relation https://elifesciences.org/articles/92136
http://crdd.osdd.net/open/3138/
 
Identifier Khan, Hina and Paul, Partha and Goar, Harsh and Bamniya, Bhanwar and Baid, Navin and Sarkar, Dibyendu (2024) Mycobacterium tuberculosis PhoP integrates stress response to intracellular survival by regulating cAMP level. ELIFE, 13.