ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1603462
This article is part of the Research TopicEmerging Antimicrobials: Sources, Mechanisms of Action, Spectrum of Activity, Combination Antimicrobial Therapy, and Resistance MechanismsView all 37 articles
Antibacterial activity and mechanism of naphthoquine phosphate against ceftazidime-resistant Acinetobacter baumannii via cell membrane disruption and ROS Induction
Provisionally accepted- 1Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing, China
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Currently, drug-resistant bacteria, particularly Acinetobacter baumannii, pose a substantial threat to global human health. In response, the urgent need for new antibacterial therapies has driven the exploration of drug reuse as a key strategy for drug development. We report that naphthoquine phosphate (NQP), an antimalarial drug, exhibits broad-spectrum antibacterial activity particular against Acinetobacter baumannii LAC-4. In the experiment, we determined the minimum inhibitory concentration (MIC) of NQP to be 62.5 µg/mL, and its inhibition kinetics curve demonstrated a concentration-dependent inhibitory effect. Our cell membrane permeability tests revealed that NQP disrupts the integrity of the cell membrane, enhancing its permeability. Furthermore, oxidative damage testing indicated that NQP impacts the metabolic processes within bacteria. NQP (62.5 µg/mL) induced significant structural damage in Acinetobacter baumannii LAC-4, as shown by TEM/SEM imaging. Key disruptions included membrane rupture, cellular deformation, and cytoplasmic disorganization. Additionally, transcriptome analysis showed that NQP disrupts multiple physiological pathways, primarily through the enhancement of cell membrane permeability and induction of oxidative stress. In conclusion, these findings suggest that NQP holds promise as a molecular scaffold for exploring novel treatment strategies for Acinetobacter baumannii infections.
Keywords: Naphthoquine phosphate, Acinetobacter baumannii, Antibacterial activity, Cell Membrane Permeability, transcriptome analysis
Received: 31 Mar 2025; Accepted: 18 Jul 2025.
Copyright: © 2025 Yuan, Zhao, Bei, Wang, Zhang, Xu, Liu, Lv, Xu and Song. 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:
Baogang Wang, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing, China
Meng Lv, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing, China
Qin Xu, Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou, 501405, China
Yabin Song, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing, China
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