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Title: hipBA toxin-antitoxin systems mediate persistence in Caulobacter crescentus
Abstract

Antibiotic persistence is a transient phenotypic state during which a bacterium can withstand otherwise lethal antibiotic exposure or environmental stresses. InEscherichia coli, persistence is promoted by the HipBA toxin-antitoxin system. The HipA toxin functions as a serine/threonine kinase that inhibits cell growth, while the HipB antitoxin neutralizes the toxin.E. coliHipA inactivates the glutamyl-tRNA synthetase GltX, which inhibits translation and triggers the highly conserved stringent response. AlthoughhipBAoperons are widespread in bacterial genomes, it is unknown if this mechanism is conserved in other species. Here we describe the functions of threehipBAmodules in the alpha-proteobacteriumCaulobacter crescentus. The HipA toxins have different effects on growth and macromolecular syntheses, and they phosphorylate distinct substrates. HipA1and HipA2contribute to antibiotic persistence during stationary phase by phosphorylating the aminoacyl-tRNA synthetases GltX and TrpS. The stringent response regulator SpoT is required for HipA-mediated antibiotic persistence, but persister cells can form in the absence of allhipBAoperons orspoT, indicating that multiple pathways lead to persister cell formation inC. crescentus.

Authors:
; ; ; ;
Publication Date:
NSF-PAR ID:
10154003
Journal Name:
Scientific Reports
Volume:
10
Issue:
1
ISSN:
2045-2322
Publisher:
Nature Publishing Group
Sponsoring Org:
National Science Foundation
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