J 2020

Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability

BOOTH, James Alexander, Mário ŠPÍREK, Tekle Airgecho LOBIE, Kirsten SKARSTAD, Lumír KREJČÍ et. al.

Basic information

Original name

Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability

Authors

BOOTH, James Alexander, Mário ŠPÍREK (703 Slovakia, guarantor, belonging to the institution), Tekle Airgecho LOBIE, Kirsten SKARSTAD, Lumír KREJČÍ (203 Czech Republic, belonging to the institution) and Magnar BJORAS

Edition

Scientific reports, London, Nature Publishing Group, 2020, 2045-2322

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.379

RIV identification code

RIV/00216224:14310/20:00114583

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1038/s41598-020-76426-2

UT WoS

000595150800002

Keywords in English

Bacteriology DNA; damage response

Tags

14110513, podil, rivok

Tags

International impact, Reviewed
Změněno: 17/3/2021 13:57, Mgr. Tereza Miškechová

Abstract

V originále

Extracellular pH has been assumed to play little if any role in how bacteria respond to antibiotics and antibiotic resistance development. Here, we show that the intracellular pH of Escherichia coli equilibrates to the environmental pH following treatment with the DNA damaging antibiotic nalidixic acid. We demonstrate that this allows the environmental pH to influence the transcription of various DNA damage response genes and physiological processes such as filamentation. Using purified RecA and a known pH-sensitive mutant variant RecA K250R we show how pH can affect the biochemical activity of a protein central to control of the bacterial DNA damage response system. Finally, two different mutagenesis assays indicate that environmental pH affects antibiotic resistance development. Specifically, at environmental pH's greater than six we find that mutagenesis plays a significant role in producing antibiotic resistant mutants. At pH's less than or equal to 6 the genome appears more stable but extensive filamentation is observed, a phenomenon that has previously been linked to increased survival in the presence of macrophages.

Links

GAP207/12/2323, research and development project
Name: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I
Investor: Czech Science Foundation
GA13-26629S, research and development project
Name: SUMO a stability genomu
Investor: Czech Science Foundation
Displayed: 12/11/2024 17:10