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Front. Microbiol. | doi: 10.3389/fmicb.2018.02846

Modification targeting the “Rana box” motif of a novel nigrocin peptide from Hylarana latouchii enhances and broadens its potency against multiple bacteria

  • 1Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, China
  • 2School of Pharmacy, Faculty of Medicine, Health and Life Sciences, Queen's University Belfast, United Kingdom

Public health is confronting threat by antibiotic resistance nowadays, and it urges us to develop new antibacterial strategies. Antimicrobial peptides (AMPs) have been considered as promising therapeutic candidates against infection in the post-antibiotic era. In this paper, nigrocin-HL was identified from skin secretion of Hylarana latouchii, and by substituting the “Rana box” sequence with a phenylalanine residue and C-terminus amidating, a shorter AMP nigrocin-HLM was obtained. Activities and toxicities of these two peptides in vitro and in vivo were compared. As a result, nigrocin-HLM not only displayed significantly increased potency against several representative microbes, but also high activity against the antibiotic-resistant methicillin-resistant S. aureus (MRSA, NCTC 12493 and ATCC43300 and several clinical isolates) as evidenced by markedly reduced minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC) and minimum biofilm eradication concentration (MBEC). More strikingly, nigrocin-HLM exhibited prominent inhibition against MRSA infection in a pneumonia mice model. In addition, the substitution attenuated the toxicity of nigrocin-HLM as evidenced by precipitously decreased hemolytic and cytotoxic activities in vitro, and acute toxicity to mice in vivo. Taken these results into consideration, nigrocin-HLM should be a promising therapeutic candidate for anti-infection. And in addition to dismiss an indispensable role of “Rana box” in maintaining antimicrobial activity of nigrocins, our data provided an inspired strategy for peptide optimization.

Keywords: nigrocin, rana box, modification, MRSA - Methicillin-resistant Staphylococcus aureus, antibiotic resistance, Pneumonia

Received: 25 Jul 2018; Accepted: 05 Nov 2018.

Edited by:

Octavio L. Franco, Universidade Católica de Brasília, Brazil

Reviewed by:

William F. Porto, Universidade Católica Dom Bosco, Brazil
Ludovico Migliolo, Universidade Católica Dom Bosco, Brazil  

Copyright: © 2018 Bao, Yuan, Ma, Wang, Hong, Xi, Zhou and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Min Hong, Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China, hongmin72@126.com