中文摘要：金黄色葡萄球菌是一种优先病原体，因为它有着越来越多的抗生素耐药性决定因素，还能在不同的生物和惰性表面形成抗性生物膜。因此，用噬菌体及其衍生的裂解蛋白帮助对抗葡萄球菌生物膜具有前瞻性。不过，这些抗菌素有着个别的局限性，可以将它们与其他化合物结合加以克服。本研究将噬菌体衍生的裂解蛋白CHAPSH3b和毒性噬菌体phiIPLA-RODI结合，显示在治疗培养了24 h的金黄色葡萄球菌生物膜时具有协同作用，与单独处理相比，联合用药后活菌数大大减少。杀菌曲线和共聚焦显微镜显示，初始暴露7小时后，CHAPSH3b的快速抗菌作用使细菌种群减少，随后噬菌体捕食，限制了细菌种群的再生。此外，至少90%的噬菌体不敏感突变体表现出对裂解蛋白敏感。因此，CHAPSH3b可能有助于抑制治疗期间噬菌体耐药性的产生。细胞溶解酶和phiIPLA-RODI的结合在猪伤口感染的体外皮肤模型中也显示出良好的效果。可见，将噬菌体衍生裂解蛋白与噬菌体结合开发改良抗菌生物膜产品可行。
外文摘要：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.
外文关键词：BACTERIOPHAGE ENDOLYSINS；BACTERIAL BIOFILMS；GENE-EXPRESSION；RESISTANCE；MASTITIS；REMOVAL；ENZYMES；BAP
作者：Duarte, AC；Fernandez, L；De Maesschalck, V；Gutierrez, D；Campelo, AB；Briers, Y Lavigne, R；Rodriguez, A；Garcia, P
作者单位：Inst Prod Lacteos Asturias IPLA CSIC；Inst Invest Sanitaria Principado Asturias ISPA；Univ Ghent；Katholieke Univ Leuven
期刊名称：NPJ BIOFILMS AND MICROBIOMES
期刊影响因子：7.067
出版年份：2021
出版刊次：1
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