BOOTH, James Alexander, Mário ŠPÍREK, Tekle Airgecho LOBIE, Kirsten SKARSTAD, Lumír KREJČÍ and Magnar BJORAS. Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability. Scientific reports. London: Nature Publishing Group, 2020, vol. 10, No 1, p. 1-18. ISSN 2045-2322. Available from: https://dx.doi.org/10.1038/s41598-020-76426-2.
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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
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher Germany
Confidentiality degree is not subject to a state or trade secret
WWW 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
Changed by Changed by: Mgr. Tereza Miškechová, učo 341652. Changed: 17/3/2021 13:57.
Abstract
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 projectName: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I
Investor: Czech Science Foundation
GA13-26629S, research and development projectName: SUMO a stability genomu
Investor: Czech Science Foundation
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