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.

Základní údaje

Originální název

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

Autoři

BOOTH, James Alexander, Mário ŠPÍREK (703 Slovensko, garant, domácí), Tekle Airgecho LOBIE, Kirsten SKARSTAD, Lumír KREJČÍ (203 Česká republika, domácí) a Magnar BJORAS

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.379

Kód RIV

RIV/00216224:14310/20:00114583

Organizační jednotka

Přírodovědecká fakulta

DOI

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

UT WoS

000595150800002

Klíčová slova anglicky

Bacteriology DNA; damage response

Štítky

14110513, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 3. 2021 13:57, Mgr. Tereza Miškechová

Anotace

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.

Návaznosti

GAP207/12/2323, projekt VaV

Název: Endonuleazová a translokázová aktivita v restričních-modifikáčních komplexéch typu I

Investor: Grantová agentura ČR, Endonuleázová a translokázová aktivita v restrikčních-modifikačních komplexech typu I

GA13-26629S, projekt VaV

Název: SUMO a stability genomu

Investor: Grantová agentura ČR, SUMO a stability genomu

Citovat

BOOTH, James Alexander, Mário ŠPÍREK, Tekle Airgecho LOBIE, Kirsten SKARSTAD, Lumír KREJČÍ a Magnar BJORAS. Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability. Scientific reports. London: Nature Publishing Group, 2020, roč. 10, č. 1, s. 1-18. ISSN 2045-2322. Dostupné z: 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 a 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, roč.~10, č.~1, s.~1-18. ISSN~2045-2322. Dostupné z: https://dx.doi.org/10.1038/s41598-020-76426-2.

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