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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F20%3A00114583" target="_blank" >RIV/00216224:14310/20:00114583 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00159816:_____/20:00073504

Výsledek na webu

<a href="https://doi.org/10.1038/s41598-020-76426-2" target="_blank" >https://doi.org/10.1038/s41598-020-76426-2</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41598-020-76426-2" target="_blank" >10.1038/s41598-020-76426-2</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Scientific reports

ISSN

2045-2322

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

18

Strana od-do

1-18

Kód UT WoS článku

000595150800002

EID výsledku v databázi Scopus

2-s2.0-85095721865