Staphylococcus aureus is considered a priority pathogen due to its increasing acquisition of antibiotic resistance determinants. Additionally, this microbe has the ability to form recalcitrant biofilms on different biotic and inert surfaces. In this context, bacteriophages and their derived lytic proteins may be a forward-looking strategy to help combat staphylococcal biofilms. However, these antimicrobials exhibit individual limitations that may be overcome by combining them with other compounds. This work investigates the combination of a phage-derived lytic protein, CHAPSH3b, and the virulent bacteriophage phiIPLA-RODI. The obtained results show the synergy between both antimicrobials for the treatment of 24-h-old S. aureus biofilms, with greater reductions in viable cell counts observed when phage and lysin are applied together compared to the individual treatments. Time-kill curves and confocal microscopy revealed that the fast antibacterial action of CHAPSH3b reduces the population up to 7 hours after initial exposure, which is subsequently followed by phage predation, limiting regrowth of the bacterial population. Moreover, at least 90% of bacteriophage insensitive mutants are susceptible to the lytic protein. Therefore, CHAPSH3b might help curtail the development of phage resistance during treatment. The combination of the lysin and phiIPLA-RODI also showed promising results in an ex vivo pig skin model of wound infection. Overall, the results of this study demonstrate that the combination of phage-derived lytic proteins and bacteriophages can be a viable strategy to develop improved antibiofilm products.

金黄色葡萄球菌被认为是优先病原体，因为它越来越多地获得抗生素耐药性决定因素。此外，这种微生物能够在不同的生物和惰性表面上形成顽固的生物膜。在这种情况下，噬菌体及其衍生的裂解蛋白可能是帮助对抗葡萄球菌生物膜的前瞻性策略。然而，这些抗微生物剂表现出个体局限性，可以通过将它们与其他化合物组合来克服。这项工作研究了噬菌体衍生的裂解蛋白 CHAPSH3b 和强毒噬菌体 phiIPLA-RODI 的组合。获得的结果表明两种抗菌剂在治疗 24 小时龄金黄色葡萄球菌方面具有协同作用生物膜，与单独处理相比，当噬菌体和溶素一起应用时观察到活细胞计数减少更多。时间-杀灭曲线和共聚焦显微镜显示，CHAPSH3b 的快速抗菌作用可在初始暴露后最多 7 小时内减少种群数量，随后是噬菌体捕食，从而限制细菌种群的再生。此外，至少 90% 的噬菌体不敏感突变体对裂解蛋白敏感。因此，CHAPSH3b 可能有助于减少治疗期间噬菌体耐药性的发展。溶素和 phiIPLA-RODI 的组合在伤口感染的离体猪皮肤模型中也显示出有希望的结果。总体，