PDF(Pubmed)
Abstract：
Metal-implant associated bacterial infections are a major clinical problem due to antibiotic treatment failure. As an alternative, we determined the effects of bacteriophage ISP on clinical isolates of Staphylococcus aureus in various stages of its life cycle in relation to biofilm formation and maturation. ISP effectively eliminated all planktonic phase bacteria, whereas its efficacy was reduced against bacteria attached to the metal implant and bacteria embedded within biofilms. The biofilm architecture hampered the bactericidal effects of ISP, as mechanical disruption of biofilms improved the efficacy of ISP against the bacteria. Phages penetrated the biofilm and interacted with the bacteria throughout the biofilm. However, most of the biofilm-embedded bacteria were phage-tolerant. In agreement, bacteria dispersed from mature biofilms of all clinical isolates, except for LUH15394, tolerated the lytic activity of ISP. Lastly, persisters within mature biofilms tolerated ISP and proliferated in its presence. Based on these findings, we conclude that ISP eliminates planktonic phase Staphylococcus aureus while its efficacy is limited against bacteria attached to the metal implant, embedded within (persister-enriched) biofilms, and dispersed from biofilms.
摘要：
由于抗生素治疗失败，金属植入物相关的细菌感染是主要的临床问题。作为替代,我们确定了噬菌体ISP对金黄色葡萄球菌临床分离株在其生命周期的各个阶段与生物膜形成和成熟有关的影响。ISP有效消除了所有浮游相细菌，而其对附着在金属植入物上的细菌和嵌入生物膜内的细菌的功效降低。生物膜结构阻碍了ISP的杀菌作用，由于生物膜的机械破坏提高了ISP对细菌的功效。噬菌体穿透生物膜并在整个生物膜中与细菌相互作用。然而,大多数生物膜包埋的细菌具有噬菌体耐受性。在协议中,从所有临床分离株的成熟生物膜中分散的细菌，除LUH15394外，耐受ISP的裂解活性。最后,成熟生物膜中的持久性细胞耐受ISP并在其存在下增殖。基于这些发现,我们得出的结论是，ISP消除了浮游期金黄色葡萄球菌，而其功效对附着在金属植入物上的细菌有限，嵌入（富含持久性的）生物膜中，并从生物膜中分散。
