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

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.

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Official URL: https://elifesciences.org/articles/92136

Abstract

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.

Item Type: Article
Additional Information: The copyright of this article belongs to MICROBIOLOGY AND INFECTIOUS DISEASE
Uncontrolled Keywords: Mycobacterium; PhoP; cAMP level; infectious disease; microbiology; stress response; virulence regulation.
Subjects: Q Science > QR Microbiology
Depositing User: Dr. K.P.S.Sengar
Date Deposited: 25 Jun 2024 03:57
Last Modified: 25 Jun 2024 03:57
URI: http://crdd.osdd.net/open/id/eprint/3138

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