期刊
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
卷 64, 期 10, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01283-20
关键词
(p)ppGpp; TA systems; persistence; slow growth
资金
- State Plan for R+D+I 2013-2016 (National Plan for Scientific Research, Technological Development and Innovation 2008-2011) [PI16/01163, PI19/00878]
- ISCIII-Deputy General Directorate for Evaluation and Promotion of Research-European Regional Development Fund, A way of Making Europe
- Instituto de Salud Carlos III FEDER
- Spanish Network for the Research in Infectious Diseases (REIPI) [RD16/0016/0006, RD16/0016/0011]
- Study Group on Mechanisms of Action and Resistance to Antimicrobials, GEMARA (SEIMC)
- Miguel Servet Research Program (SERGAS)
- Miguel Servet Research Program (ISCIII)
- Diputation A Coruna (Xunta Galicia)
- National Health and Medical Research Council [GNT1088448]
Antibiotic failure not only is due to the development of resistance by pathogens but can also often be explained by persistence and tolerance. Persistence and tolerance can be included in the persistent phenotype, with high relevance for clinics. Two of the most important molecular mechanisms involved in tolerance and persistence are toxin-antitoxin (TA) modules and signaling via guanosine pentaphosphate/tetraphosphate [(p)ppGpp], also known as magic spot. (p)ppGpp is a very important stress alarmone which orchestrates the stringent response in bacteria; hence, (p)ppGpp is produced during amino acid or fatty acid starvation by proteins belonging to the RelA/SpoT homolog family (RSH). However, (p)ppGpp levels can also accumulate in response to a wide range of signals, including oxygen variation, pH downshift, osmotic shock, temperature shift, or even exposure to darkness. Furthermore, the stringent response is not only involved in responses to environmental stresses (starvation for carbon sources, fatty acids, and phosphates or heat shock), but it is also used in bacterial pathogenesis, host invasion, and antibiotic tolerance and persistence. Given the exhaustive and contradictory literature surrounding the role of (p)ppGpp in bacterial persistence, and with the aim of summarizing what is known so far about the magic spot in this bacterial stage, this review provides new insights into the link between the stringent response and persistence. Moreover, we review some of the innovative treatments that have (p)ppGpp as a target, which are in the spotlight of the scientific community as candidates for effective antipersistence agents.
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