Stringent Response in Mycobacteria: From Biology to Therapeutic Potential

Pathogens

Kuldeepkumar Ramnaresh Gupta¹  Abid Mattoo²  Gunjan Arora³  Andaleeb Sajid³ 

[1] Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520, USA;Pharmaceutical Development, Ultragenyx Gene Therapy, Woburn, MA 01801, USA;Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA;

关键词: Mycobacterium;    alarmones;    (pp)pGpp. Rel;    RelZ;    stress response;    drug resistance;   

DOI  :  10.3390/pathogens10111417

来源: DOAJ

【 摘 要 】

Mycobacterium tuberculosis is a human pathogen that can thrive inside the host immune cells for several years and cause tuberculosis. This is due to the propensity of M. tuberculosis to synthesize a sturdy cell wall, shift metabolism and growth, secrete virulence factors to manipulate host immunity, and exhibit stringent response. These attributes help M. tuberculosis to manage the host response, and successfully establish and maintain an infection even under nutrient-deprived stress conditions for years. In this review, we will discuss the importance of mycobacterial stringent response under different stress conditions. The stringent response is mediated through small signaling molecules called alarmones “(pp)pGpp”. The synthesis and degradation of these alarmones in mycobacteria are mediated by Rel protein, which is both (p)ppGpp synthetase and hydrolase. Rel is important for all central dogma processes—DNA replication, transcription, and translation—in addition to regulating virulence, drug resistance, and biofilm formation. Rel also plays an important role in the latent infection of M. tuberculosis. Here, we have discussed the literature on alarmones and Rel proteins in mycobacteria and highlight that (p)ppGpp-analogs and Rel inhibitors could be designed and used as antimycobacterial compounds against M. tuberculosis and non-tuberculous mycobacterial infections.

【 授权许可】

Unknown