hipBA toxin-antitoxin systems mediate persistence in Caulobacter crescentus
Artikel i vetenskaplig tidskrift, 2020

Antibiotic persistence is a transient phenotypic state during which a bacterium can withstand otherwise lethal antibiotic exposure or environmental stresses. In Escherichia 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. coli HipA inactivates the glutamyl-tRNA synthetase GltX, which inhibits translation and triggers the highly conserved stringent response. Although hipBA operons are widespread in bacterial genomes, it is unknown if this mechanism is conserved in other species. Here we describe the functions of three hipBA modules in the alpha-proteobacterium Caulobacter crescentus. The HipA toxins have different effects on growth and macromolecular syntheses, and they phosphorylate distinct substrates. HipA1 and HipA2 contribute 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 all hipBA operons or spoT, indicating that multiple pathways lead to persister cell formation in C. crescentus.

Författare

Charlie Y. Huang

University of California at Berkeley

Carlos Gonzalez-Lopez

University of California at Berkeley

Céline Henry

Université Paris-Saclay

Ivan Mijakovic

Chalmers, Biologi och bioteknik, Systembiologi

Danmarks Tekniske Universitet (DTU)

Kathleen R. Ryan

University of California at Berkeley

Scientific Reports

2045-2322 (ISSN)

Vol. 10 1 2865

Ämneskategorier

Cellbiologi

Cell- och molekylärbiologi

Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

DOI

10.1038/s41598-020-59283-x

PubMed

32071324

Mer information

Senast uppdaterat

2020-03-04