Design of �-hairpin peptides with potent antimicrobial activity and target specificity against Enterococcus faecalis

Abstract

Event Abstract Back to Event Design of β-hairpin peptides with potent antimicrobial activity and target specificity against Enterococcus faecalis Lin Xu1, 2, Anshan Shan1, Changxuan Shao1, Qingquan Ma1, Dong Na1, Shuli Chou1 and Jiajun Wang1 1 Institute of Animal Nutrition, Northeast Agricultural University, China 2 Heilongjiang Polytechnic, Heilongjiang Polytechnic, China Most classical antibiotics have broad spectra of activity, killing benign and pathogenic organisms indiscriminately. The ecological disruption resulting from antibiotic treatment frequently results in secondary infections or other negative clinical consequences. The problems resulting from wide-spectrum antibiotic use, combined with the emergence of drug-resistant strains, highlight the fundamental need for new “targeted” antibiotic therapies to combat pathogens with a minimal impact on normal microflora. Antimicrobial peptides (AMPs), which exert their activities by physical disruption of microbial cell membranes are amongst the most promising candidates for the development of novel antibacterial materials. Recently, we developed a new class of linear tryptophan zipper (trpzip)-like β-hairpin AMPs, which possess antimicrobial activities against both gram-positive and gram-negative bacteria. In the present study, a series of Enterococcus faecalis-targeted AMPs were constructed as a model for targeted antibiotics against specific bacteria. To target the broad-spectrum AMPs to the cell membranes of E. faecalis, the enterococcal peptide pheromone cCF10 was linked to the N-terminus or the C-terminus of trpzip peptides, respectively. This pheromone cCF10 is a species-specific signaling molecule could traverse the cell wall and bind to its receptor with a high affinity. The results showed that the hybrid peptides containing enterococcal pheromone at the N terminus exhibit greatly enhanced antimicrobial activities and selectivity against E. faecalis when compared to the parental peptides. The specificity of pheromonicin was shown by a dose-dependent inhibition of the antimicrobial effects of hybrid peptides by competition with free cCF10 pheromone. Similarly, a construct in which a random peptide of the same length as cCF10 fused to the N terminus of trpzip peptides did not exhibit any inhibitory effects to targeted bacteria. These results indicate that the specifically antimicrobial activities of the designed peptides against E. faecalis are receptor dependent. Electron microscopy and fluorescence spectroscopy studies indicated that pheromone-guided hybrid peptides exert their activities by permeabilizing the microbial membrane and damaging cell membrane integrity. This study provides new insights into the design of targeted antimicrobial peptides which could selectively eliminate pathogens while preserving the protective benefits of a healthy normal flora. the National Natural Research Foundation of China (31272453, 31472104); the National Basic Research Program (Grant no. 2012CB124703) Keywords: Bacteria, biomaterial, Biocompatibility, Polypeptide Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Anti-infective biomaterials Citation: Xu L, Shan A, Shao C, Ma Q, Na D, Chou S and Wang J (2016). Design of β-hairpin peptides with potent antimicrobial activity and target specificity against Enterococcus faecalis. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.00354 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lin Xu Anshan Shan Changxuan Shao Qingquan Ma Dong Na Shuli Chou Jiajun Wang Google Lin Xu Anshan Shan Changxuan Shao Qingquan Ma Dong Na Shuli Chou Jiajun Wang Google Scholar Lin Xu Anshan Shan Changxuan Shao Qingquan Ma Dong Na Shuli Chou Jiajun Wang PubMed Lin Xu Anshan Shan Changxuan Shao Qingquan Ma Dong Na Shuli Chou Jiajun Wang Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.