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Screening for a Potent Antibacterial Peptide to Treat Mupirocin-Resistant MRSA Skin Infections

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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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Acknowledgements

This work was supported by the A*STAR Biomedical Research Council (Singapore).

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  1. Experimental Therapeutics Centre, Agency for Science, Technology and Research (A*STAR), 31 Biopolis Way, Nanos #03-01, Singapore, 138669, Singapore

    Siew Mei Samantha Ng, Hui Si Vivian Ching, GuiFang Xu, Fui Mee Ng, Esther H. Q. Ong, Qiu Ying Lau, Jeffrey Hill & C. S. Brian Chia

  2. Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore

    Roland Jureen

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  1. Siew Mei Samantha Ng
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Siew Mei Samantha Ng, Hui Si Vivian Ching, and GuiFang Xu have contributed equally to this work.

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Ng, S.M.S., Ching, H.S.V., Xu, G. et al. Screening for a Potent Antibacterial Peptide to Treat Mupirocin-Resistant MRSA Skin Infections. Int J Pept Res Ther 23, 481–491 (2017). https://doi.org/10.1007/s10989-017-9580-x

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