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Bacillus subtilis produces(p)ppGpp in response to the bacteriostatic antibiotic chloramphenicol to prevent its potential bactericidal effect

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mLife 2022年第2期1卷 101-113页

作者： Jin Yang Jessica T.Barra Danny K.Fung Jue D.Wang Department of Bacteriology University of WisconsinMadisonUSA

antibiotics combat bacteria through their bacteriostatic(by growth inhibition)or bactericidal(by killing bacteria)***,it has been proposed that bactericidal antibiotics trigger cellular damage,while bacteriostatic antibiotics suppress cellular ***,we demonstrate how the difference between bacteriostatic and bactericidal activities of the antibiotic chloramphenicol can be attributed to an antibiotic-induced bacterial protective response:the stringent *** targets the ribosome to inhibit the growth of the Gram-positive bacterium Bacillus ***,we found that chloramphenicol becomes bactericidal in *** mutants unable to produce(p)*** observed a similar(p)ppGpp-dependent bactericidal effect of chloramphenicol in the Gram-positive pathogen Enterococcus *** ***,chloramphenicol treatment induces(p)ppGpp accumulation through the action of the(p)ppGpp synthetase RelA.(p)ppGpp subsequently depletes the intracellular concentration of GTP and antagonizes GTP *** GTP regulation is critical for preventing chloramphenicol from killing ***,as bypassing(p)ppGpp-dependent GTP regulation potentiates chloramphenicol killing,while reducing GTP synthesis increases ***,chloramphenicol treatment protects cells from the classical bactericidal antibiotic vancomycin,reminiscent of the clinical phenomenon of antibiotic *** together,our findings suggest a role of(p)ppGpp in the control of the bacteriostatic and bactericidal activity of antibiotics in Gram-positive bacteria,which can be exploited to potentiate the efficacy of existing antibiotics.

关键词： antibiotic tolerance bactericidal antibiotic bacteriostatic antibiotic GTP (p)ppGpp

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Regrowth-delay Body as a Bacterial Subcellular Structure Marking Multidrug Tolerant Persisters

Regrowth-delay Body as a Bacterial Subcellular Structure Mar...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2...

作者： Jiayu Yu Yang Liu Huijia Yin Zengyi Chang School of Life Sciences Peking University

Bacteria have been known to be able to enter a non-growing state when encountering unfit conditions,termed *** take a variable lag time and exhibit multidrug tolerance before resuming growth when placed in growth-supportive conditions,thus posing a great challenge in treating infectious *** to their non-inheritability,low abundance of existence,lack of metabolic activities,and high heterogeneity,properties of persisters remain poorly ***,we report our accidental discovery of a subcellular structure that we termed the regrowth-delay body,which is formed in nongrowing bacterial cells and sequesters selected proteins essential for cell *** formation occurs progressively in each cell and heterogeneously among individual *** only disassemble in re-growing cells to release proteins for immediate re-functioning when conditions become *** regrowth-delay bodies apparently function as a biological timer for bacterial growth resumption and could mark the multidrug tolerant *** observations implicate that persisters exhibit different depth of persistence,as determined by the status of their regrowth-delay *** findings also implicate that suppressing the formation and/or promoting the disassembly of regrowth-delay bodies are viable strategies for eradicating persisters.

关键词： Regrowth-delay body Lag time FtsZ antibiotic tolerance

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