Publication details

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

Investor logo
Investor logo

BOOTH James Alexander ŠPÍREK Mário LOBIE Tekle Airgecho SKARSTAD Kirsten KREJČÍ Lumír BJORAS Magnar

Year of publication 2020
Type Article in Periodical
Magazine / Source Scientific reports
MU Faculty or unit

Faculty of Science

Keywords Bacteriology DNA; damage response
Description 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.
Related projects:

You are running an old browser version. We recommend updating your browser to its latest version.

More info