Hfq influences ciprofloxacin accumulation in Escherichia coli independently of ompC and ompF post-transcriptional regulation.

Journal of applied genetics [J Appl Genet] 2025 May; Vol. 66 (2), pp. 449-457. Date of Electronic Publication: 2025 Feb 08.

Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
The antibiotic resistance of pathogenic bacteria is currently one of the major problems in medicine, and finding novel antibacterial agents is one of the most difficult tasks in the field of biomedical sciences. Studies on such tasks can be successful only if genetic and molecular mechanisms leading to antibiotic resistance/sensitivity are understood. Previous reports indicated that the bacterial protein Hfq, discovered as an RNA chaperone but subsequently demonstrated to play also other functions in cells, is involved in the mechanisms of the response of bacterial cells to antibiotics. Recently, it was found that Hfq dysfunction resulted in more effective accumulation of an antibiotic ciprofloxacin in Escherichia coli cells irrespective of the presence or absence of the AcrB efflux pump. However, small RNA-mediated impairment of expression of the ompF gene, which encodes a porin involved in antibiotics influx, reversed the effects of the absence of Hfq on the antibiotic accumulation. This led to the hypothesis that Hfq might influence ciprofloxacin accumulation in the manner independent on its RNA chaperone function, as this protein might also influence cellular membrane structure and functions. Here, we demonstrate that in ompC and ompF mutants of E. coli, accumulation of ciprofloxacin is significantly impaired in the absence of Hfq or its C-terminal domain. These results corroborate the above-mentioned hypothesis on a sRNA-independent mechanism of Hfq-mediated modulation of the antibiotic transmembrane transport. Since fluoroquinolones use both protein- and lipid-mediated pathways to cross the outer membrane, Hfq may influence both processes. This possibility will be discussed herein.
(© 2025. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.)

English

Publisher: Springer Country of Publication: England NLM ID: 9514582 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2190-3883 (Electronic) Linking ISSN: 12341983 NLM ISO Abbreviation: J Appl Genet Subsets: MEDLINE

Ciprofloxacin*/pharmacology , Ciprofloxacin*/metabolism , Host Factor 1 Protein*/genetics , Host Factor 1 Protein*/metabolism , Escherichia coli Proteins*/genetics , Escherichia coli Proteins*/metabolism , Escherichia coli*/genetics , Escherichia coli*/metabolism , Escherichia coli*/drug effects , Porins*/genetics , Porins*/metabolism, Gene Expression Regulation, Bacterial ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/metabolism

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