التفاصيل البيبلوغرافية
العنوان: |
Exploring in vitro efficacy of rCHAPk with antibiotic combinations, and promising findings of its therapeutic potential for clinical-originated MRSA wound infection |
المؤلفون: |
Tasdurmazli, Semra, Cinar, Irfan, Karamese, Murat, Aksak Karamese, Selina, Cadirci, Elif, Melo, Luís Daniel Rodrigues, Ozbek, Tulin |
المساهمون: |
Universidade do Minho |
بيانات النشر: |
Elsevier, 2025. |
سنة النشر: |
2025 |
مصطلحات موضوعية: |
Endolysin rCHAPk, Endolysin-antibiotic synergism, MRSA-infected in vivo wound model |
الوصف: |
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 g of rCHAPk reduced OD600 by 0.4 within 5 min against a clinical methicillin-resistant S. aureus (MRSA) strain. Combining rCHAPk (1.875 g/mL) with oxacillin/vancomycin lowered their minimum bactericidal concentrations to 1 g/mL from initial values over 64 g/mL and 32 g/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. © 2025 Elsevier B.V. |
نوع الوثيقة: |
journal article |
وصف الملف: |
application/pdf |
اللغة: |
English |
Relation: |
Tasdurmazli, Semra; Cinar, Irfan; Karamese, Murat; Aksak Karamese, Selina; Cadirci, Elif; Melo, Luís Daniel Rodrigues; Ozbek, Tulin, Exploring in vitro efficacy of rCHAPk with antibiotic combinations, and promising findings of its therapeutic potential for clinical-originated MRSA wound infection. International Journal of Biological Macromolecules, 296(139630), 2025; 0141-8130; http://www.elsevier.com/locate/issn/01418130 |
DOI: |
10.1016/j.ijbiomac.2025.139630 |
الاتاحة: |
https://hdl.handle.net/1822/94658 |
Rights: |
open access |
رقم الانضمام: |
rcaap.com.repositorium.repositorium.sdum.uminho.pt.1822.94658 |
قاعدة البيانات: |
RCAAP |