PMID- 33329494 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201218 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 11 DP - 2020 TI - Anti-infective Effects of a Fish-Derived Antimicrobial Peptide Against Drug-Resistant Bacteria and Its Synergistic Effects With Antibiotic. PG - 602412 LID - 10.3389/fmicb.2020.602412 [doi] LID - 602412 AB - Antimicrobial peptides (AMPs) play pivotal roles in protecting against microbial infection in fish. However, AMPs from topmouth culter (Erythroculter ilishaeformis) are rarely known. In our study, we isolated an AMP from the head kidney of topmouth culter, which belonged to liver-expressed antimicrobial peptide 2 (LEAP-2) family. Topmouth culter LEAP-2 showed inhibitory effects on aquatic bacterial growth, including antibiotic-resistant bacteria, with minimal inhibitory concentration values ranging from 18.75 to 150 mug/ml. It was lethal for Aeromonas hydrophila (resistant to ampicillin), and took less than 60 min to kill A. hydrophila at a concentration of 5 x MIC. Scanning electron microscope (SEM) and SYTOX Green uptake assay indicated that it impaired the integrity of bacterial membrane by eliciting pore formation, thereby increasing the permeabilization of bacterial membrane. In addition, it showed none inducible drug resistance to aquatic bacteria. Interestingly, it efficiently delayed ampicillin-induced drug resistance in Vibrio parahaemolyticus (sensitive to ampicillin) and sensitized ampicillin-resistant bacteria to ampicillin. The chequerboard assay indicated that topmouth culter LEAP-2 generated synergistic effects with ampicillin, indicating the combinational usage potential of topmouth culter LEAP-2 with antibiotics. As expected, topmouth culter LEAP-2 significantly alleviated ampicillin-resistant A. hydrophila infection in vivo, and enhanced the therapeutic efficacy of ampicillin against A. hydrophila in vivo. Our findings provide a fish innate immune system-derived peptide candidate for the substitute of antibiotics and highlight its potential for application in antibiotic-resistant bacterial infection in aquaculture industry. CI - Copyright (c) 2020 Chen, Wu, Cheng, Dai, Wang, Yang, Xiong, Xu and Wei. FAU - Chen, Yue AU - Chen Y AD - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. FAU - Wu, Jing AU - Wu J AD - School of Basic Medical Sciences, Kunming Medical University, Kunming, China. FAU - Cheng, Honglan AU - Cheng H AD - The Second Affiliated Hospital of Soochow University, Suzhou, China. FAU - Dai, Yue AU - Dai Y AD - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. FAU - Wang, Yipeng AU - Wang Y AD - Department of Biopharmaceuticals, College of Pharmaceutical Sciences, Soochow University, Suzhou, China. FAU - Yang, Hailong AU - Yang H AD - The Second Affiliated Hospital of Soochow University, Suzhou, China. FAU - Xiong, Fei AU - Xiong F AD - The Second Affiliated Hospital of Soochow University, Suzhou, China. FAU - Xu, Wei AU - Xu W AD - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. FAU - Wei, Lin AU - Wei L AD - Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou, China. LA - eng PT - Journal Article DEP - 20201123 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC7719739 OTO - NOTNLM OT - Erythroculter ilishaeformis OT - antimicrobial peptide OT - aquatic bacteria OT - drug resistance OT - liver-expressed antimicrobial peptide 2 OT - synergistic effect EDAT- 2020/12/18 06:00 MHDA- 2020/12/18 06:01 PMCR- 2020/11/23 CRDT- 2020/12/17 05:50 PHST- 2020/09/04 00:00 [received] PHST- 2020/10/28 00:00 [accepted] PHST- 2020/12/17 05:50 [entrez] PHST- 2020/12/18 06:00 [pubmed] PHST- 2020/12/18 06:01 [medline] PHST- 2020/11/23 00:00 [pmc-release] AID - 10.3389/fmicb.2020.602412 [doi] PST - epublish SO - Front Microbiol. 2020 Nov 23;11:602412. doi: 10.3389/fmicb.2020.602412. eCollection 2020.