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

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

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

Citovat

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.

@article{1710936,
   author = {Booth, James Alexander and Špírek, Mário and Lobie, Tekle Airgecho and Skarstad, Kirsten and Krejčí, Lumír and Bjoras, Magnar},
   article_location = {London},
   article_number = {1},
   doi = {http://dx.doi.org/10.1038/s41598-020-76426-2},
   keywords = {Bacteriology DNA; damage response},
   language = {eng},
   issn = {2045-2322},
   journal = {Scientific reports},
   title = {Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability},
   url = {https://doi.org/10.1038/s41598-020-76426-2},
   volume = {10},
   year = {2020}
}

TY  - JOUR
ID  - 1710936
AU  - Booth, James Alexander - Špírek, Mário - Lobie, Tekle Airgecho - Skarstad, Kirsten - Krejčí, Lumír - Bjoras, Magnar
PY  - 2020
TI  - Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability
JF  - Scientific reports
VL  - 10
IS  - 1
SP  - 1-18
EP  - 1-18
PB  - Nature Publishing Group
SN  - 20452322
KW  - Bacteriology DNA
KW  - damage response
UR  - https://doi.org/10.1038/s41598-020-76426-2
L2  - https://doi.org/10.1038/s41598-020-76426-2
N2  - 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.
ER  -

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. \textit{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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