ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicBacterial Metabolites: Redefining Strategies to Combat Antimicrobial ResistanceView all 7 articles
Integration host factor regulates antibiotic susceptibility through modulating alanine metabolism in Escherichia coli
Provisionally accepted
- Sun Yat-sen University, Guangzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Purpose: This study aimed to define how integration host factor (IHF) influences antibiotic susceptibility through metabolic regulation, using Escherichia coli ΔihfA and ΔihfB mutants. Methods: The metabolic profiles of ΔihfA and ΔihfB mutants were analyzed by gas chromatography-mass spectrometry (GC-MS) versus the K12 parent. Antibiotic susceptibility was assessed by plate counting, proton motive force (PMF) by flow cytometry, and enzyme activities via 3-(4,5-Dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide (MTT) reduction. Results: Deletion of ihfA and ihfB resulted in increased minimum inhibitory concentrations (MICs) and/or enhanced bacterial survival upon exposure to ampicillin, balofloxacin, or gentamicin. Both mutants exhibited global metabolic downregulation, with significantly reduced alanine levels identified as the most prominent biomarker. Consistent with these observations, enzymatic activities in the pyruvate cycle were impaired, and PMF was diminished. Exogenous alanine supplementation restored the pyruvate cycle and PMF level, thereby resensitizing the mutants to all three antibiotics. This effect was further corroborated by the use of the PMF inhibitor carbonyl cyanide m-chlorophenyl hydrazone, which abolished alanine-mediated antibiotic killing in ΔihfA and ΔihfB strains. Conclusions: Together, these results provide compelling evidence that IHF modulates antibiotic susceptibility through metabolic reprogramming, with alanine metabolism and PMF maintenance serving as key functional links.
Keywords: Alanine, antibiotic susceptibility, Integration host factor, Metabolism, reprogramming metabolomics
Received: 04 Aug 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Li, Fu, Jiang and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hui Li
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.