| Persisters are small subpopulation of low-metabolism dormant bacteria that can survive in fatal stress. Critically, retention microbes may be one of major causes of antibiotic treatment failure and recurrent infections. Toxin-antitoxin systems (TA), as stress-responsive modules, are ubiquitous among various bacteria and are composed of a stable toxin and a labile homologous antitoxin that neutralizes toxin. Under stress, the second messenger (p)ppGpp activates Lon, and most type II TA is subsequently activated, inducing the formation of retention microbes. Similarly, under the presence of (p)ppGpp, Obg mediates persistence by stimulating hokB transcription to increase the accumulation of toxin, which inhibits bacterial DNA replication, transcription, translation and other important physiological processes. Another major pathway to activate the TA is SOS response that unrepressed the transcription of tisB, allowing it to accumulate and insert into cell membranes, destroy proton dynamic potential, reduce intracellular ATP levels, and induce the formation of dormant and retention microbes. This article discusses the mechanism of TA mediating the formation of retention microbes, which would conduce to propose multiple novel antibacterial strategies. |
