Screening for a Potent Antibacterial Peptide to Treat Mupirocin-Resistant MRSA Skin Infections |
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Authors: | Siew Mei Samantha Ng Hui Si Vivian Ching GuiFang Xu Fui Mee Ng Esther H. Q. Ong Qiu Ying Lau Roland Jureen Jeffrey Hill C. S. Brian Chia |
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Affiliation: | 1.Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR),Singapore,Singapore;2.Department of Laboratory Medicine,National University Hospital,Singapore,Singapore |
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Abstract: | Mupirocin is the first-line topical antibacterial drug for treating skin infections caused primarily by meticillin-resistant Staphylococcus aureus (MRSA). Its widespread use since its introduction more than 30 years ago has resulted in the global emergence of mupirocin-resistant strains of MRSA. Antimicrobial peptides (AMPs) are a promising class of antibacterial compounds that can potentially be developed to replace mupirocin due to their rapid membrane-targeting bactericidal mode of action and predicted low propensity for resistance development. Herein, we conducted and compared the antibacterial activities of 61 AMPs between 3 and 11 residues in length reported in the literature over the past decade against mupirocin-resistant MRSA. The most potent AMP, 11-residue peptide 50, was selected and tested against a panel of clinical isolates followed by a time-kill and a human dermal keratinocyte cytotoxicity assay. Lastly, peptide 50 was formulated into a topical spray which showed strong in vitro bactericidal effects against mupirocin-resistant MRSA. Our results strongly suggest that peptide 50 has the potential to be further developed into a new class of topical antibacterial agent for treating drug-resistant MRSA skin infections. |
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