ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1681222
This article is part of the Research TopicIntegrating Health: a One Health Approach to Antimicrobial Resistance and Sustainable PracticesView all 10 articles
The dltC Contributes to Polyhexamethylene Biguanide Resistance in Staphylococcus aureus
Provisionally accepted
Chenyang Guo1,2Congcong Wang3Qihui Chen4
Sophia Hao Zheng5Fengji Zhang1Jiayu Yan6Haoyang Brady Long7Jing Luo1Xiaoyan Xuan1
Peng Wang1
Huaixin Zheng1*- 1Zhengzhou University, Zhengzhou, China
- 2Fudan University Eye Ear Nose and Throat Hospital Department of Ophthalmology, Shanghai, China
- 3Jilin University Key Laboratory of Pathobiology Ministry of Education, Changchun, China
- 4Wuhan University Medical Research Institute, Wuhan, China
- 5Keystone Academy, 11 An Fu Street, Hou Sha Yu, Shunyi District, Beijing, Beijing, China
- 6University of California Davis, Davis, United States
- 7Nanjing Foreign Language School, Nanjing 210008, China, Nanjing, China
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As the efficacy of conventional antibiotics continues to decline due to antibiotic resistance, there is an urgent need for alternative antimicrobial strategies. Polyhexamethylene biguanide (PHMB), a cationic polymer with broad-spectrum antimicrobial activity and low toxicity, has been extensively used in medical and personal care applications. Although no definitive cases of bacterial resistance to PHMB have been reported, resistance to other cationic agents suggests the potential resistance to PHMB. In this study, Staphylococcus aureus was cultivated in the presence of a sublethal concentration of PHMB for 30 days, during which the organism developed inheritable resistance. A quantitative proteomics study identified differential expression of the DltC protein, which is associated with cell wall biosynthesis. Our findings revealed structural and chemical alterations in the bacterial cell wall, resulting in a surface with increased hydrophobicity, which leads to PHMB resistance. Furthermore, the adaptive PHMB-resistant strains exhibited elevated sensitivity to the hydrophobic antibiotic chloramphenicol and enhanced resistance to the hydrophilic antibiotics gentamicin and kanamycin, consistent with the resistance mechanism uncovered in this study. These results provide new insights into potential resistance mechanisms against PHMB and offer a foundation for its rational use and future antimicrobial development.
Keywords: Staphylococcus aureus, PHMB, Bacterial resistance, Dlt operon, hydrophobicity
Received: 07 Aug 2025; Accepted: 10 Oct 2025.
Copyright: © 2025 Guo, Wang, Chen, Zheng, Zhang, Yan, Long, Luo, Xuan, Wang and Zheng. 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: Huaixin Zheng, huaixin_zheng@zzu.edu.cn
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