ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1648096
This article is part of the Research TopicImmunomodulatory Strategies in Perioperative Organ Protection: From Mitochondrial Dysfunction to Clinical ApplicationsView all articles
Effect of Daphnetin Combined with Tobramycin on Pseudomonas aeruginosa Biofilm Infection In Vitro and In Vivo
Provisionally accepted
Dingbin Li1
Chao Mao1Siyuan Chen1Zhongwei Wang1Weilin Zhang1
Zhencong Li1Liangsheng Li1
Chaoqin He1Weixiong Guo1
Jinsong Wei1Qingjun Wei2*- 1Affiliated Hospital of Guangdong Medical University, Zhanjiang, China
- 2The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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Objective: The aim of this study was to investigate the effectiveness of daphnetin in combination with tobramycin on Pseudomonas aeruginosa biofilm infection in vitro and in vivo.The study was divided into four groups: control, tobramycin, daphnetin, and tobramycin combined with daphnetin groups. First, a 72-h Pseudomonas aeruginosa biofilm model was established in vitro. The antibacterial effects of daphnetin and tobramycin alone and in combination were evaluated using various methods, including microdilution, crystal violet staining, colony counting, and electron microscopy. Then, a model of Pseudomonas aeruginosa biofilm infection in rabbit joints was established in vivo. After 7 days of continuous treatment, the rabbits were sacrificed on day 14 postinfection. The therapeutic effect of daphnetin and/or tobramycin was further evaluated by observing the gross anatomy of the knee joint, biofilm PNA-FISH, synovial bacterial load, and pathology.Results: The results showed that daphnetin had a minimum inhibition concentration (MIC) of 890 µg/mL against the PAO1 strain, while tobramycin had an MIC of 2.75 µg/mL against the same strain. Crystal violet staining and colony counting showed that the biofilm in the group treated with both daphnetin and tobramycin was significantly less than that in the control group (P < 0.05). Scanning electron microscopy further confirmed that the combination of daphnetin and tobramycin had the strongest bactericidal effect. In vivo, the knee joint of rabbits in the daphnetin combined with tobramycin group had the least gross anatomical inflammatory response, amount of PNA-FISH biofilm, synovial colony count, synovial pathological examination of inflammatory cell infiltration, and synovial thickening. Conclusion: The study indicated that daphnetin may be a promising synergist that enhances the activity of tobramycin against Pseudomonas aeruginosa biofilm infection in vitro and in vivo.
Keywords: Daphnetin, Biofilm, Tobramycin, Pseudomonas aeruginosa, combination
Received: 16 Jun 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Li, Mao, Chen, Wang, Zhang, Li, Li, He, Guo, Wei and Wei. 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: Qingjun Wei, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
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