ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
This article is part of the Research TopicInnovative Immunological Strategies for Overcoming Antimicrobial Resistance and Enhancing Vaccine DevelopmentView all 9 articles
Phenothiazines enhance antibacterial activity of macrophage by inducing ROS and autophagy
Provisionally accepted
- College of Veterinary Medicine, Jilin University, Changchun, China
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Bacterial infections pose a major global public health threat. While antibiotics have historically served as the primary treatment, the rapid rise of antibiotic resistance has led to an urgent need for new therapeutic strategies. Host-directed therapies (HDTs), which activate defense mechanisms of host cells, are emerging as a promising alternative. Host-acting compounds (HACs) have no direct effect on bacteria and therefore do not induce drug resistance or alter intestinal microbiota composition. In the present study, we demonstrated that phenothiazines significantly enhance the antibacterial capacity of macrophages. In macrophages treated with phenothiazines, we observed a significant increase in lysosomal activity, induction of autophagy, and accumulation of reactive oxygen species (ROS). Importantly, co-treatment with autophagy inhibitors or ROS scavengers markedly diminished the antibacterial effects of phenothiazines. Furthermore, perphenazine (PHZ) effectively reduced organ lesions and inflammation associated with S. Typhimurium infections in vivo. Our results demonstrated that phenothiazines are lead compounds for antibacterial agents via HDTs.
Keywords: Phenothiazines, Intracellular bacteria, HdtS, ROS, Autophagy
Received: 25 Sep 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Qiu, Chen, Wang, Deng, Liu and Qiu. 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:
Hongtao Liu, liuht2018@jlu.edu.cn
Jiazhang Qiu, qiujz@jlu.edu.cn
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