Academic Journal
Photodynamic and antibiotic combination therapy against multidrug-resistant Pseudomonas aeruginosa wound infections in diabetic rats.
| Τίτλος: | Photodynamic and antibiotic combination therapy against multidrug-resistant Pseudomonas aeruginosa wound infections in diabetic rats. |
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| Συγγραφείς: | Kong F; School of Basic Medical Sciences, Hebei University, Baoding, China; Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, China., Zhang T; School of Basic Medical Sciences, Hebei University, Baoding, China., Liu Y; The Second Surgical Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China., Li Y; School of Clinical Medicine, Hebei University, Baoding, China., Liu X; School of Basic Medical Sciences, Hebei University, Baoding, China., Bai C; School of Basic Medical Sciences, Hebei University, Baoding, China., Wang T; School of Clinical Medicine, Hebei University, Baoding, China., Zhao Z; School of Basic Medical Sciences, Hebei University, Baoding, China. Electronic address: zhaozhanjuanv@163.con., Hong G; Tianjin Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, China. Electronic address: hongge@bme.pumc.edu.cn. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109955. Date of Electronic Publication: 2026 May 09. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Anti-Bacterial Agents*/pharmacology , Anti-Bacterial Agents*/chemistry , Pseudomonas aeruginosa*/drug effects , Diabetes Mellitus, Experimental*/drug therapy , Wound Infection*/drug therapy , Wound Infection*/microbiology , Pseudomonas Infections*/drug therapy , Ceftazidime*/pharmacology , Ceftazidime*/chemistry , Photosensitizing Agents*/pharmacology , Photosensitizing Agents*/chemistry , Aminolevulinic Acid*/pharmacology , Aminolevulinic Acid*/chemistry , Photochemotherapy*, Drug Resistance, Multiple, Bacterial/drug effects ; Wound Healing/drug effects ; Animals ; Rats ; Microbial Sensitivity Tests ; Male ; Rats, Sprague-Dawley ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Structure-Activity Relationship ; Molecular Structure |
| Περίληψη: | In our previous study, 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) promoted chronic diabetic wound healing by reducing the microbial burden. However, the anti-bacterial efficacy of ALA-PDT is often compromised by limited light penetration into tissues. To increase the efficacy of ALA-PDT, this study assessed its combined use with the antibiotic ceftazidime in treating chronic diabetic wounds and examined the potential mechanism of action. The results indicated that the combination of ALA-PDT and ceftazidime synergistically inhibited the growth of multidrug-resistant Pseudomonas aeruginosa. The treatment also prevented the formation of bacterial biofilm, delayed the development of antibiotic resistance, inactivated pyocyanin, and exerted a prolonged post-antibiotic effect. The mechanism supporting the synergistic antibacterial effect might involve ALA-PDT-mediated reactive oxygen species generation, leading to bacterial cell structure destruction, increased membrane permeability, and cellular ceftazidime uptake. In a full-thickness skin defect infection model in rats with diabetes, the bactericidal and wound closure rates were highest in the combination therapy group. Transcriptomics analysis of wound tissues revealed that the differentially expressed genes between the combination therapy and model groups were mainly enriched in the IL-17, AKT-STAT, and VEGF signaling pathways. Molecular biology experiments illustrated that the combination therapy might regulate the expression of IL-17, activate the JAK-STAT axis, increase p-JAK2 and p-STAT3 expression, and decrease SOCS3 expression, ultimately leading to Ki-67, CD31, and VEGF upregulation and exerting beneficial effects on angiogenesis, collagen deposition, and tissue regeneration. Overall, PDT and antibiotic combination therapy offers an efficient approach to treat infections in diabetic wounds. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: 5-aminolevulinic acid; Ceftazidime; Diabetes wound; Photodynamic therapy |
| Substance Nomenclature: | 0 (Anti-Bacterial Agents) 9M416Z9QNR (Ceftazidime) 0 (Photosensitizing Agents) 88755TAZ87 (Aminolevulinic Acid) |
| Entry Date(s): | Date Created: 20260513 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.bioorg.2026.109955 |
| PMID: | 42127741 |
| Βάση Δεδομένων: | MEDLINE |
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