Guanosine tetra- and pentaphosphate increase antibiotic tolerance by reducing reactive oxygen species production in Vibrio cholerae

The Journal of Biological Chemistry
Hwa Young KimSang Sun Yoon

Abstract

The pathogen Vibrio cholerae is the causative agent of cholera. Emergence of antibiotic-resistant V. cholerae strains is increasing, but the underlying mechanisms remain unclear. Herein, we report that the stringent response regulator and stress alarmone guanosine tetra- and pentaphosphate ((p)ppGpp) significantly contributes to antibiotic tolerance in V. cholerae We found that N16961, a pandemic V. cholerae strain, and its isogenic (p)ppGpp-overexpressing mutant ΔrelAΔspoT are both more antibiotic-resistant than (p)ppGpp0 (ΔrelAΔrelVΔspoT) and ΔdksA mutants, which cannot produce or utilize (p)ppGpp, respectively. We also found that additional disruption of the aconitase B-encoding and tricarboxylic acid (TCA) cycle gene acnB in the (p)ppGpp0 mutant increases its antibiotic tolerance. Moreover, expression of TCA cycle genes, including acnB, was increased in (p)ppGpp0, but not in the antibiotic-resistant ΔrelAΔspoT mutant, suggesting that (p)ppGpp suppresses TCA cycle activity, thereby entailing antibiotic resistance. Importantly, when grown anaerobically or incubated with an iron chelator, the (p)ppGpp0 mutant became antibiotic-tolerant, suggesting that reactive oxygen species (ROS) are involved in antibiotic-mediated bacterial...Continue Reading

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Citations

Sep 7, 2019·Proceedings of the National Academy of Sciences of the United States of America·Shilpa Elizabeth GeorgeChristiane Wolz
Aug 11, 2019·Molecular Microbiology·Anurag Kumar SinhaKenn Gerdes
Feb 13, 2020·The Journal of Antimicrobial Chemotherapy·Hye-Won JungMinsang Shin
Sep 22, 2020·Journal of Environmental Science and Health. Part C, Toxicology and Carcinogenesis·Prabin ShresthaTit-Yee Wong
Nov 10, 2020·Frontiers in Microbiology·Bhabatosh Das, Rupak K Bhadra
Feb 2, 2021·Frontiers in Cellular and Infection Microbiology·Wolfgang EisenreichWerner Goebel
Dec 22, 2020·Frontiers in Microbiology·Shivani KundraJosé A Lemos
Jul 10, 2019·ACS Infectious Diseases·Joanne K Hobbs, Alisdair B Boraston
Oct 15, 2021·Frontiers in Microbiology·Lizhen SiJiaoyu Deng

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