PMID- 34025617 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210526 IS - 1664-302X (Print) IS - 1664-302X (Electronic) IS - 1664-302X (Linking) VI - 12 DP - 2021 TI - A Chimeric Cationic Peptide Composed of Human beta-Defensin 3 and Human beta-Defensin 4 Exhibits Improved Antibacterial Activity and Salt Resistance. PG - 663151 LID - 10.3389/fmicb.2021.663151 [doi] LID - 663151 AB - Human beta-defensins (hBDs) play an important role in the host defense against various microbes, showing different levels of antibacterial activity and salt resistance in vitro. It is of interest to investigate whether can chimeric hBD analogs enhanced antibacterial activity and salt resistance. In this study, we designed a chimeric human defensin, named H4, by combining sequences of human beta-defensin-3 (hBD-3) and human beta-defensin-4 (hBD-4), then evaluated its antibacterial activity, salt resistance, and cytotoxic effects. The result showed that the antibacterial activity of H4 against most tested strains, including Klebsiella pneumonia, Enterococcus faecalis, Staphyloccocus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, and Acinetobacter baumannii was significantly improved compared to that of hBD-3 and hBD-4. Notably, H4 exhibited significantly better antibacterial activity against multidrug resistant isolate A. baumannii MDR-ZJ06 than commonly used antibiotics. Chimeric H4 still showed more than 80% antibacterial activity at high salt concentration (150 muM), which proves its good salt tolerance. The cytotoxic effect assay showed that the toxicity of H4 to Hela, Vero, A549 cells and erythrocytes at a low dose (<10 mug/ml) was similar to that of hBD-3 and hBD-4. In conclusion, given its broad spectrum of antibacterial activity and high salt resistance, chimeric H4 could serve as a promising template for new therapeutic antimicrobial agents. CI - Copyright (c) 2021 Yu, Ning, Xue, Huang, Guo, Li, Yang, Luo, Sun, Li, Wang, He, Cheng, Zhang and Wang. FAU - Yu, Wenjing AU - Yu W AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Ning, Nianzhi AU - Ning N AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Xue, Ying AU - Xue Y AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. AD - College of Life Science, Ludong University, Yantai, China. FAU - Huang, Yanyu AU - Huang Y AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Guo, Feng AU - Guo F AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Li, Tao AU - Li T AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Yang, Boning AU - Yang B AD - Department of Orthopedics, Henan University People's Hospital, Zhengzhou, China. FAU - Luo, Deyan AU - Luo D AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Sun, Yakun AU - Sun Y AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Li, Zhan AU - Li Z AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Wang, Jianxin AU - Wang J AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - He, Zhili AU - He Z AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. FAU - Cheng, Shiwei AU - Cheng S AD - College of Life Science, Ludong University, Yantai, China. FAU - Zhang, Xingxiao AU - Zhang X AD - College of Life Science, Ludong University, Yantai, China. FAU - Wang, Hui AU - Wang H AD - State Key Laboratory of Pathogens and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China. LA - eng PT - Journal Article DEP - 20210507 PL - Switzerland TA - Front Microbiol JT - Frontiers in microbiology JID - 101548977 PMC - PMC8137984 OTO - NOTNLM OT - antibacterial activity OT - chimeric human defensin OT - human beta-defensins OT - multidrug resistant OT - salt resistance COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/25 06:00 MHDA- 2021/05/25 06:01 PMCR- 2021/05/07 CRDT- 2021/05/24 08:04 PHST- 2021/02/02 00:00 [received] PHST- 2021/04/14 00:00 [accepted] PHST- 2021/05/24 08:04 [entrez] PHST- 2021/05/25 06:00 [pubmed] PHST- 2021/05/25 06:01 [medline] PHST- 2021/05/07 00:00 [pmc-release] AID - 10.3389/fmicb.2021.663151 [doi] PST - epublish SO - Front Microbiol. 2021 May 7;12:663151. doi: 10.3389/fmicb.2021.663151. eCollection 2021.