Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification

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RESEARCH ARTICLE

Open Access

Enhancing the antibacterial activity of antimicrobial peptide PMAP-37(F34-R) by cholesterol modification Liangliang Chen1†, Tengfei Shen1†, Yongqing Liu1, Jiangfei Zhou1, Shuaibing Shi1, Yang Wang2, Zhanqin Zhao1,2, Zhiling Yan3, Chengshui Liao1,2* and Chen Wang1,2*

Abstract Background: The problem of increasing resistance against conventional antibiotics has drawn people’s attention. Therefore, the development of novel antibacterial agents with effective and safe therapeutic effects is imminent. Antimicrobial peptides (AMPs) are considered a promising class of antibacterial agents due to their broad antibacterial spectrum. Results: In this study, on the basis of our previously studied peptide PMAP-37(F34-R), a novel antimicrobial peptide Chol-37(F34-R) was developed by N-terminal cholesterol modification to increase hydrophobicity. We observed that the N-terminal cholesterol-modified Chol-37(F34-R) showed higher antimicrobial activity than PMAP-37(F34-R) in vitro. Chol-37(F34-R) also exhibited effective anti-biofilm activity and may kill bacteria by improving the permeability of their membranes. Chol-37(F34-R) exerted high stability in different pH, salt, serum, and boiling water environments. Chol-37(F34-R) also showed no hemolytic activity and substantially low toxicity. Furthermore, Chol-37(F34-R) exhibited good potency of bacteria eradication and promoted wound healing and abscess reduction in infected mice. Meanwhile, in S. aureus ATCC25923-infected peritonitis model, Chol-37(F34-R) exhibited an impressive therapeutic effect by reducing the decrease in systemic bacterial burden and alleviating organ damage. Conclusions: Our findings suggested that the N-terminal cholesterol modification of PMAP-37(F34-R) could improve antibacterial activity. Chol-37(F34-R) displayed excellent bactericidal efficacy and impressive therapeutic effect in vivo. Thus, Chol-37(F34-R) may be a candidate for antimicrobial agents against microbial infection in the clinic. Keywords: Antimicrobial peptide PMAP-37(F34-R), Cholesterol, Hydrophobicity, Antibacterial activity, Therapeutic efficacy

* Correspondence: [email protected]; [email protected] † Liangliang Chen and Tengfei Shen contributed equally to this work. 1 The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, Henan, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative

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