Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway.
Department of Plant Molecular Biology, Norwegian Institute of Bioeconomy Research, Ås, Norway.
Antimicrob Agents Chemother. 2020 Nov 17;64(12). doi: 10.1128/AAC.00829-20.
The emergence of antibiotic-resistant pathogens has caused a serious worldwide problem in infection treatment in recent years. One of the pathogens is methicillin-resistant (MRSA), which is a major cause of skin and soft tissue infections. Alternative strategies and novel sources of antimicrobials to solve antibiotic resistance problems are urgently needed. In this study, we explored the potential of two broad-spectrum bacteriocins, garvicin KS and micrococcin P1, in skin infection treatments. The two bacteriocins acted synergistically with each other and with penicillin G in killing MRSA The MICs of the antimicrobials in the three-component mixture were 40 ng/ml for micrococcin P1 and 2 μg/ml for garvicin KS and penicillin G, which were 62, 16, and at least 1,250 times lower than their MICs when assessed individually. To assess its therapeutic potential further, we challenged the three-component formulation in a murine skin infection model with the multidrug-resistant luciferase-tagged MRSA Xen31, a strain derived from the clinical isolate ATCC 33591. Using the tagged-luciferase activity as a reporter for the presence of Xen31 in wounds, we demonstrated that the three-component formulation was efficient in eradicating the pathogen from treated wounds. Furthermore, compared to Fucidin cream, which is an antibiotic commonly used in skin infection treatments, our formulation was also superior in terms of preventing resistance development.
近年来,抗生素耐药病原体的出现导致了感染治疗方面的全球性严重问题。其中一种病原体是耐甲氧西林金黄色葡萄球菌(MRSA),它是皮肤和软组织感染的主要原因。急需寻找替代策略和新型抗菌药物来解决抗生素耐药问题。在这项研究中,我们探索了两种广谱细菌素——garvicin KS 和 micrococcin P1 在皮肤感染治疗中的潜力。这两种细菌素相互协同,与青霉素 G 一起杀死 MRSA。三种成分混合物中抗菌药物的 MIC 值为:micrococcin P1 为 40ng/ml,garvicin KS 和青霉素 G 为 2μg/ml,与单独评估时相比,MIC 值分别降低了 62、16 和至少 1250 倍。为了进一步评估其治疗潜力,我们用多药耐药荧光素标记的 MRSA Xen31 (一种源自临床分离株 ATCC 33591 的菌株)在小鼠皮肤感染模型中对三种成分制剂进行了挑战。我们利用标记的荧光素活性作为伤口中 Xen31 存在的报告,证明了三种成分制剂能够有效地从治疗伤口中根除病原体。此外,与常用于皮肤感染治疗的抗生素 Fucidin 乳膏相比,我们的制剂在预防耐药性发展方面也具有优势。