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Exploring in vitro efficacy of rCHAPk with antibiotic combinations, and promising findings of its therapeutic potential for clinical-originated MRSA wound infection    
Yazarlar (7)
Semra Tasdurmazli
Yıldız Teknik Üniversitesi, Turkey
Doç. Dr. İrfan ÇINAR Doç. Dr. İrfan ÇINAR
Kastamonu Üniversitesi, Türkiye
Murat Karamese
Kafkas Üniversitesi, Turkey
Selina Aksak Karamese
Kafkas Üniversitesi, Turkey
Elif Cadirci
Ataturk University, Faculty of Medicine, Turkey
Luís D.R. Melo
Universidade do Minho, Portugal
Tulin Ozbek
Yıldız Teknik Üniversitesi, Turkey
Devamını Göster
Özet
The increasing threat of antimicrobial-resistant bacteria, particularly Staphylococcus aureus, which rapidly develops multidrug resistance and commonly colonizes wound surfaces, demands innovative strategies. Phage-encoded endolysins offer a dual-purpose approach as topical therapies for infectious skin wounds and synergistic agents to reduce high-dose antibiotic dependence. This study explores recombinant CHAPk (rCHAPk), efficiently synthesized within 3 h, displaying broad-spectrum antibacterial activity against 10 Gram-positive strains, including resistant variants, with rapid bactericidal kinetics. Application of 10 μg of rCHAPk reduced OD600 by 0.4 within 5 min against a clinical methicillin-resistant S. aureus (MRSA) strain. Combining rCHAPk (1.875 μg/mL) with oxacillin/vancomycin lowered their minimum bactericidal concentrations to 1 μg/mL from initial values over 64 μg/mL and 32 μg/mL, respectively, with a fractional inhibitory concentration index below 0.1. rCHAPk retained efficacy after one year of refrigerated storage. In in vivo experiments, rCHAPk outperformed commercial fucidin therapy in MRSA-induced murine wound models over two weeks, enhancing wound healing by modulating pro-inflammatory cytokine responses and the proliferative phase. This study, for the first time, investigates rCHAPk's in vitro combination with antibiotics and wound healing parameters, highlighting its potential as a potent antibacterial agent synergizing with antibiotics to address antibiotic-resistant bacterial wound infections.
Anahtar Kelimeler
Endolysin rCHAPk | Endolysin-antibiotic synergism | MRSA-infected in vivo wound model
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı International Journal of Biological Macromolecules
Dergi ISSN 0141-8130
Dergi Grubu Q1
Makale Dili İngilizce
Basım Tarihi 03-2025
Cilt No 296
Sayı 1
Doi Numarası 10.1016/j.ijbiomac.2025.139630