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Membrane-Active Amphipathic Peptide WRL3 with in Vitro Antibiofilm Capability and in Vivo Efficacy in Treating Methicillin-Resistant Staphylococcus aureus Burn Wound Infections
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2017-09-18 00:00:00 , DOI: 10.1021/acsinfecdis.7b00100 Zhi Ma 1 , Jinzhi Han 1 , Bingxue Chang 1 , Ling Gao 1 , Zhaoxin Lu 1 , Fengxia Lu 1 , Haizhen Zhao 1 , Chong Zhang 1 , Xiaomei Bie 1
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2017-09-18 00:00:00 , DOI: 10.1021/acsinfecdis.7b00100 Zhi Ma 1 , Jinzhi Han 1 , Bingxue Chang 1 , Ling Gao 1 , Zhaoxin Lu 1 , Fengxia Lu 1 , Haizhen Zhao 1 , Chong Zhang 1 , Xiaomei Bie 1
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Methicillin-resistant Staphylococcus aureus (MRSA) has become increasingly prevalent in hospitals, clinics, and the community. MRSA can cause significant and even lethal infections, especially in skin burn wounds. The currently available topical agents have largely failed to eliminate MRSA infections due to resistance. Therefore, there is an urgent need for new and effective approaches for treating MRSA. Here, we show that a novel engineered amphipathic peptide, WRL3 (WLRAFRRLVRRLARGLRR-NH2), exhibits potent antimicrobial activity against MRSA, even in the presence of various salts or serum. The cell selectivity of WRL3 was demonstrated by its ability to specifically eliminate MRSA cells over host cells in a coculture model. Additionally, WRL3 showed a synergistic effect against MRSA when combined with ceftriaxone and effectively inhibited sessile biofilm bacteria growth leading to a reduction in biomass. Fluorescent measurements and microscopic observations of live bacterial cells and artificial membranes revealed that WRL3 exerted its bactericidal activity possibly by destroying the bacterial membrane. In vivo studies indicate that WRL3 is able to control proliferation of MRSA in wound tissue and reduce bioburden and provides a more favorable environment for wound healing. Collectively, our data suggest that WRL3 has enormous potential as a novel antimicrobial agent for the treatment of clinical MRSA infections of skin burn wounds.
中文翻译：
膜活性两亲性肽WRL3具有体外抗生物膜能力和体内功效，可治疗耐甲氧西林的金黄色葡萄球菌烧伤创面感染。
耐甲氧西林金黄色葡萄球菌（MRSA）在医院，诊所和社区中变得越来越普遍。MRSA可能导致严重甚至致命的感染，尤其是在皮肤烧伤创面中。由于抗药性，目前可用的局部用药在很大程度上未能消除MRSA感染。因此，迫切需要用于治疗MRSA的新的有效方法。在这里，我们显示了一种新型的工程两亲肽WRL3（WLRAFRRLVRRLARGLRR-NH2），即使在存在各种盐或血清的情况下，也表现出了针对MRSA的有效抗菌活性。在共培养模型中，WRL3具有比宿主细胞特异性消除MRSA细胞的能力，从而证明了WRL3的细胞选择性。此外，当与头孢曲松联合使用时，WRL3显示出对MRSA的协同作用，并有效抑制了固着生物膜细菌的生长，导致生物量减少。荧光测量和活细菌细胞和人造膜的显微镜观察显示，WRL3可能通过破坏细菌膜发挥其杀菌活性。体内研究表明，WRL3能够控制伤口组织中MRSA的增殖并减少生物负荷，并为伤口愈合提供了更有利的环境。总体而言，我们的数据表明WRL3作为一种新型抗菌剂具有巨大的潜力，可用于治疗皮肤烧伤创面的临床MRSA感染。
更新日期：2017-09-18
中文翻译：
膜活性两亲性肽WRL3具有体外抗生物膜能力和体内功效，可治疗耐甲氧西林的金黄色葡萄球菌烧伤创面感染。
耐甲氧西林金黄色葡萄球菌（MRSA）在医院，诊所和社区中变得越来越普遍。MRSA可能导致严重甚至致命的感染，尤其是在皮肤烧伤创面中。由于抗药性，目前可用的局部用药在很大程度上未能消除MRSA感染。因此，迫切需要用于治疗MRSA的新的有效方法。在这里，我们显示了一种新型的工程两亲肽WRL3（WLRAFRRLVRRLARGLRR-NH2），即使在存在各种盐或血清的情况下，也表现出了针对MRSA的有效抗菌活性。在共培养模型中，WRL3具有比宿主细胞特异性消除MRSA细胞的能力，从而证明了WRL3的细胞选择性。此外，当与头孢曲松联合使用时，WRL3显示出对MRSA的协同作用，并有效抑制了固着生物膜细菌的生长，导致生物量减少。荧光测量和活细菌细胞和人造膜的显微镜观察显示，WRL3可能通过破坏细菌膜发挥其杀菌活性。体内研究表明，WRL3能够控制伤口组织中MRSA的增殖并减少生物负荷，并为伤口愈合提供了更有利的环境。总体而言，我们的数据表明WRL3作为一种新型抗菌剂具有巨大的潜力，可用于治疗皮肤烧伤创面的临床MRSA感染。
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