دورية أكاديمية

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

التفاصيل البيبلوغرافية
العنوان: Antibiotic-induced DNA damage results in a controlled loss of pH homeostasis and genome instability.
المؤلفون: Booth JA; Department of Microbiology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. james.booth@rr-research.no., Špírek M; Department of Biology, Masaryk University, Kamenice 5/A7, 625 00, Brno, Czech Republic.; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic., Lobie TA; Department of Microbiology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway., Skarstad K; Department of Microbiology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway., Krejci L; Department of Biology, Masaryk University, Kamenice 5/A7, 625 00, Brno, Czech Republic.; National Centre for Biomolecular Research, Masaryk University, Kamenice 5/A4, 625 00, Brno, Czech Republic.; International Clinical Research Center, Center for Biomolecular and Cellular Engineering, St. Anne's University Hospital Brno, Pekarska 53, 656 91, Brno, Czech Republic., Bjørås M; Department of Microbiology, University of Oslo and Oslo University Hospital, Rikshospitalet, Oslo, Norway. magnar.bjoras@rr-research.no.; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. magnar.bjoras@rr-research.no.
المصدر: Scientific reports [Sci Rep] 2020 Nov 10; Vol. 10 (1), pp. 19422. Date of Electronic Publication: 2020 Nov 10.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Anti-Bacterial Agents/*pharmacology , DNA Damage/*drug effects , DNA Damage/*genetics , Escherichia coli/*drug effects , Escherichia coli/*genetics , Genomic Instability/*drug effects , Genomic Instability/*genetics, DNA Damage/radiation effects ; Electrophoretic Mobility Shift Assay ; Escherichia coli/radiation effects ; Flow Cytometry ; Genomic Instability/radiation effects ; Hydrogen-Ion Concentration ; Microbial Viability/drug effects ; Microbial Viability/radiation effects ; Nalidixic Acid/pharmacology ; Propidium/pharmacology ; Rifampin/pharmacology ; Ultraviolet Rays
مستخلص: 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.
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المشرفين على المادة: 0 (Anti-Bacterial Agents)
36015-30-2 (Propidium)
3B91HWA56M (Nalidixic Acid)
VJT6J7R4TR (Rifampin)
تواريخ الأحداث: Date Created: 20201111 Date Completed: 20210514 Latest Revision: 20210514
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7655802
DOI: 10.1038/s41598-020-76426-2
PMID: 33173044
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-020-76426-2