SigE: A master regulator of Mycobacterium tuberculosis

Frontiers in Microbiology

Microbiology

Roberta Provvedi¹  Agnese Serafini²  Riccardo Manganelli²  Davide Sorze²  Marta Conflitti²  Francesca Boldrin²  Greta Segafreddo²  Laura Cioetto-Mazzabò² 

[1] Department of Biology, University of Padova, Padova, Italy;Department of Molecular Medicine, University of Padova, Padova, Italy;

关键词: Mycobacterium tuberculosis;    sigma factor;    stress response;    regulatory network;    pathogenesis;   

DOI  :  10.3389/fmicb.2023.1075143

 received in 2022-10-20, accepted in 2023-02-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

The Extracellular function (ECF) sigma factor SigE is one of the best characterized out of the 13 sigma factors encoded in the Mycobacterium tuberculosis chromosome. SigE is required for blocking phagosome maturation and full virulence in both mice and guinea pigs. Moreover, it is involved in the response to several environmental stresses as surface stress, oxidative stress, acidic pH, and phosphate starvation. Underscoring its importance in M. tuberculosis physiology, SigE is subjected to a very complex regulatory system: depending on the environmental conditions, its expression is regulated by three different sigma factors (SigA, SigE, and SigH) and a two-component system (MprAB). SigE is also regulated at the post-translational level by an anti-sigma factor (RseA) which is regulated by the intracellular redox potential and by proteolysis following phosphorylation from PknB upon surface stress. The set of genes under its direct control includes other regulators, as SigB, ClgR, and MprAB, and genes involved in surface remodeling and stabilization. Recently SigE has been shown to interact with PhoP to activate a subset of genes in conditions of acidic pH. The complex structure of its regulatory network has been suggested to result in a bistable switch leading to the development of heterogeneous bacterial populations. This hypothesis has been recently reinforced by the finding of its involvement in the development of persister cells able to survive to the killing activity of several drugs.

【 授权许可】

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Copyright © 2023 Manganelli, Cioetto-Mazzabò, Segafreddo, Boldrin, Sorze, Conflitti, Serafini and Provvedi.