skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms

Abstract

Research highlights: {yields} Short antimicrobial peptides with nine and eleven residues were developed. {yields} These peptides show strong bactericidal activity against clinically important bacterial and fungal pathogens. {yields} These peptides exhibit high stability in the presence of salts, and low cytotoxicity. {yields} These peptides exert their action by disrupting membrane lipids. -- Abstract: Short antimicrobial peptides with nine and eleven residues were developed against several clinically important bacterial and fungal pathogens (specifically Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Fusarium solani). Twelve analogues of previously reported peptides BP76 (KKLFKKILKFL) and Pac-525 (KWRRWVRWI) were designed, synthesized, and tested for their antimicrobial activities. Two of our eleven amino acid peptides, P11-5 (GKLFKKILKIL) and P11-6 (KKLIKKILKIL), have very low MICs of 3.1-12.5 {mu}g ml{sup -1} against all five pathogens. The MICs of these two peptides against S. aureus, C. albicans and F. solani are four to ten times lower than the corresponding MICs of the reference peptide BP76. P9-4 (KWRRWIRWL), our newly designed nine-amino acid analogue, also has particularly low MICs of 3.1-6.2 {mu}g ml{sup -1} against four of the tested pathogens; these MICs are two to eight times lower than those reported for Pac-525 (6.2-50 {mu}g ml{sup -1}).These new peptidesmore » (P11-5, P11-6 and P9-4) also exhibit improved stability in the presence of salts, and have low cytotoxicity as shown by the hemolysis and MTT assays. From the results of field-emission scanning electron microscopy, membrane depolarization and dye-leakage assays, we propose that these peptides exert their action by disrupting membrane lipids. Molecular dynamics simulation studies confirm that P11-6 peptide maintains relatively stable helical structure and exerts more perturbation action on the order of acyl tail of lipid bilayer.« less

Authors:
; ;  [1];  [2]; ; ; ; ;  [1];  [3];  [2];  [1]
  1. School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore (Singapore)
  2. School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore (Singapore)
  3. Menicon Co., Ltd. Immeuble Espace Cordeliers, 2, rue President Carnot, 69002 Lyon (France)
Publication Date:
OSTI Identifier:
22202723
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 398; Journal Issue: 3; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CANDIDA; DEPOLARIZATION; ESCHERICHIA COLI; FUSARIUM; HEMOLYSIS; LIPIDS; MOLECULAR DYNAMICS METHOD; PATHOGENS; PEPTIDES; PERTURBATION THEORY; PERTURBED ANGULAR CORRELATION; PSEUDOMONAS; SCANNING ELECTRON MICROSCOPY; STAPHYLOCOCCUS; TOXICITY

Citation Formats

Qi, Xiaobao, Zhou, Chuncai, Li, Peng, Xu, Weixin, Cao, Ye, Ling, Hua, Ning Chen, Wei, Ming Li, Chang, Xu, Rong, Lamrani, Mouad, Mu, Yuguang, Leong, Susanna Su Jan, Wook Chang, Matthew, E-mail: matthewchang@ntu.edu.sg, and Chan-Park, Mary B., E-mail: mbechan@ntu.edu.sg. Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms. United States: N. p., 2010. Web. doi:10.1016/J.BBRC.2010.06.131.
Qi, Xiaobao, Zhou, Chuncai, Li, Peng, Xu, Weixin, Cao, Ye, Ling, Hua, Ning Chen, Wei, Ming Li, Chang, Xu, Rong, Lamrani, Mouad, Mu, Yuguang, Leong, Susanna Su Jan, Wook Chang, Matthew, E-mail: matthewchang@ntu.edu.sg, & Chan-Park, Mary B., E-mail: mbechan@ntu.edu.sg. Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms. United States. https://doi.org/10.1016/J.BBRC.2010.06.131
Qi, Xiaobao, Zhou, Chuncai, Li, Peng, Xu, Weixin, Cao, Ye, Ling, Hua, Ning Chen, Wei, Ming Li, Chang, Xu, Rong, Lamrani, Mouad, Mu, Yuguang, Leong, Susanna Su Jan, Wook Chang, Matthew, E-mail: matthewchang@ntu.edu.sg, and Chan-Park, Mary B., E-mail: mbechan@ntu.edu.sg. 2010. "Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms". United States. https://doi.org/10.1016/J.BBRC.2010.06.131.
@article{osti_22202723,
title = {Novel short antibacterial and antifungal peptides with low cytotoxicity: Efficacy and action mechanisms},
author = {Qi, Xiaobao and Zhou, Chuncai and Li, Peng and Xu, Weixin and Cao, Ye and Ling, Hua and Ning Chen, Wei and Ming Li, Chang and Xu, Rong and Lamrani, Mouad and Mu, Yuguang and Leong, Susanna Su Jan and Wook Chang, Matthew, E-mail: matthewchang@ntu.edu.sg and Chan-Park, Mary B., E-mail: mbechan@ntu.edu.sg},
abstractNote = {Research highlights: {yields} Short antimicrobial peptides with nine and eleven residues were developed. {yields} These peptides show strong bactericidal activity against clinically important bacterial and fungal pathogens. {yields} These peptides exhibit high stability in the presence of salts, and low cytotoxicity. {yields} These peptides exert their action by disrupting membrane lipids. -- Abstract: Short antimicrobial peptides with nine and eleven residues were developed against several clinically important bacterial and fungal pathogens (specifically Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Fusarium solani). Twelve analogues of previously reported peptides BP76 (KKLFKKILKFL) and Pac-525 (KWRRWVRWI) were designed, synthesized, and tested for their antimicrobial activities. Two of our eleven amino acid peptides, P11-5 (GKLFKKILKIL) and P11-6 (KKLIKKILKIL), have very low MICs of 3.1-12.5 {mu}g ml{sup -1} against all five pathogens. The MICs of these two peptides against S. aureus, C. albicans and F. solani are four to ten times lower than the corresponding MICs of the reference peptide BP76. P9-4 (KWRRWIRWL), our newly designed nine-amino acid analogue, also has particularly low MICs of 3.1-6.2 {mu}g ml{sup -1} against four of the tested pathogens; these MICs are two to eight times lower than those reported for Pac-525 (6.2-50 {mu}g ml{sup -1}).These new peptides (P11-5, P11-6 and P9-4) also exhibit improved stability in the presence of salts, and have low cytotoxicity as shown by the hemolysis and MTT assays. From the results of field-emission scanning electron microscopy, membrane depolarization and dye-leakage assays, we propose that these peptides exert their action by disrupting membrane lipids. Molecular dynamics simulation studies confirm that P11-6 peptide maintains relatively stable helical structure and exerts more perturbation action on the order of acyl tail of lipid bilayer.},
doi = {10.1016/J.BBRC.2010.06.131},
url = {https://www.osti.gov/biblio/22202723}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 398,
place = {United States},
year = {Fri Jul 30 00:00:00 EDT 2010},
month = {Fri Jul 30 00:00:00 EDT 2010}
}