Gupta Kuldeepkumar Ramnaresh, Arora Gunjan, Mattoo Abid, Sajid Andaleeb
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06520, USA.
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
Pathogens. 2021 Nov 1;10(11):1417. doi: 10.3390/pathogens10111417.
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 to synthesize a sturdy cell wall, shift metabolism and growth, secrete virulence factors to manipulate host immunity, and exhibit stringent response. These attributes help 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 . 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 and non-tuberculous mycobacterial infections.
是一种人类病原体，可在宿主免疫细胞内存活数年并引发结核病。这是由于其倾向于合成坚固的细胞壁、改变代谢和生长、分泌毒力因子以操纵宿主免疫并表现出严谨反应。这些特性有助于应对宿主反应，甚至在营养匮乏的应激条件下也能成功建立并维持感染数年。在本综述中，我们将讨论分枝杆菌严谨反应在不同应激条件下的重要性。严谨反应是由称为警报素“(pp)pGpp”的小信号分子介导的。分枝杆菌中这些警报素的合成和降解由Rel蛋白介导，Rel蛋白既是(ppGpp)合成酶又是水解酶。Rel除了调节毒力、耐药性和生物膜形成外，对所有中心法则过程——DNA复制、转录和翻译——都很重要。Rel在的潜伏感染中也起着重要作用。在此，我们讨论了分枝杆菌中警报素和Rel蛋白的相关文献，并强调可以设计(p)ppGpp类似物和Rel抑制剂并将其用作抗分枝杆菌化合物来对抗和非结核分枝杆菌感染。
