Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, NY 10065, USA.
Antimicrob Agents Chemother. 2011 Feb;55(2):738-44. doi: 10.1128/AAC.00890-10. Epub 2010 Nov 22.
Staphylococcus aureus is a major human pathogen responsible for a number of serious and sometimes fatal infections. One of its reservoirs on the human body is the skin, which is known to be a source of invasive infection. The potential for an engineered staphylococcus-specific phage lysin (ClyS) to be used for topical decolonization is presented. We formulated ClyS into an ointment and applied it to a mouse model of skin colonization/infection with S. aureus. Unlike the standard topical antibacterial agent mupirocin, ClyS eradicated a significantly greater number of methicillin-susceptible S. aureus (MSSA) and -resistant S. aureus (MRSA) bacteria: a 3-log reduction with ClyS as opposed to a 2-log reduction with mupirocin in our model. The use of ClyS also demonstrated a decreased potential for the development of resistance by MRSA and MSSA organisms compared to that from the use of mupirocin in vitro. Because antibodies may affect enzyme function, we tested antibodies developed after repeated ClyS exposure for their effect on ClyS killing ability. Our results showed no inhibition of ClyS activity at various antibody titers. These data demonstrate the potential of developing ClyS as a novel class of topical antimicrobial agents specific to staphylococcus.
金黄色葡萄球菌是一种主要的人类病原体，可导致许多严重甚至致命的感染。人体上的一个储存库是皮肤，众所周知，皮肤是侵袭性感染的来源。本文提出了一种针对金黄色葡萄球菌的工程化特异性噬菌体溶素（ClyS）用于局部去定植的潜力。我们将 ClyS 制成软膏，并将其应用于金黄色葡萄球菌皮肤定植/感染的小鼠模型。与标准局部抗菌剂莫匹罗星不同，ClyS 能更有效地消除大量耐甲氧西林金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）细菌：我们的模型中，ClyS 可使细菌减少 3 个对数级，而莫匹罗星则减少 2 个对数级。与莫匹罗星相比，ClyS 的使用还表明，MRSA 和 MSSA 细菌产生耐药性的潜力降低。由于抗体可能影响酶的功能，我们测试了在重复 ClyS 暴露后产生的抗体对 ClyS 杀伤能力的影响。我们的结果表明，在不同的抗体滴度下，ClyS 活性没有受到抑制。这些数据表明，开发 ClyS 作为一种新型的针对金黄色葡萄球菌的局部抗菌药物具有潜力。
