In silico design of polycationic antimicrobial peptides active against Pseudomonas aeruginosa and Staphylococcus aureus
Antimicrobial peptides (AMPs) have the potential to become valuable antimicrobial drugs in the coming years, since they offer wide spectrum of action, rapid bactericidal activity, and low probability for resistance development in comparison with traditional antibiotics. The search and improvement of methodologies for discovering new AMPs to treat resistant bacteria such as Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa are needed for further development of antimicrobial products. In this work, the software Peptide ID 1.0® was used to find new antimicrobial peptide candidates encrypted in proteins, considering the physicochemical parameters characteristics of AMPs such as positive net charge, hydrophobicity, and sequence length, among others. From the selected protein fragments, new AMPs were designed after conservative and semi-conservative modifications and amidation of the C-terminal region. In vitro studies of the antimicrobial activity of the newly designed peptides showed that two peptides, P3-B and P3-C, were active against P. aeruginosa Escherichia coli and A. baumannii with low minimum inhibitory concentrations. Peptide P3-C was also active against K. pneumoniae and S. aureus. Furthermore, bactericidal activity and information on the possible mechanisms of action are described according to the scanning electron microscopy studies.
KeywordsCationic antimicrobial peptides Bioinformatics Peptide design Pseudomonas aeruginosa Staphylococcus aureus
This research has been funded by projects 9727 and 35058 from Universidad Nacional de Colombia, sede Medellin.
Conflict of interest
The authors declare that they have no conflict of interest.
- Amaral AC, Silva ON, Mundim NCCC, de Carvalho MJ, Migliolo L, Leite JR, Prates MV, Bocca AL, Franco OL, Felipe MS (2012) Predicting antimicrobial peptides from eukaryotic genomes: in silico strategies to develop antibiotics. Peptides 37:301–308. https://doi.org/10.1016/j.peptides.2012.07.021 CrossRefPubMedGoogle Scholar
- Berditsch M, Jäger T, Strempel N, Schwartz T, Overhage J, Ulrich AS (2015) Synergistic effect of membrane-active peptides polymyxin B and gramicidin S on multidrug-resistant strains and biofilms of Pseudomonas aeruginosa. Antimicrob Agents Chemother 59:5288–5296. https://doi.org/10.1128/AAC.00682-15 CrossRefPubMedPubMedCentralGoogle Scholar
- Fauchere J-L, Pliska V (1983) Hydrophobic parameters pi of amino-acid side chains from the partitioning of N-acetyl-amino-acid amides. Eur J Med Chem Chim Ther 18:369–375Google Scholar
- Malagoli D (2007) A full-length protocol to test hemolytic activity of palytoxin on human erythrocytes. Invertebr Surv J 4:92–94Google Scholar
- Rieg S, Huth A, Kalbacher H, Kern WV (2009) Resistance against antimicrobial peptides is independent of Escherichia coli AcrAB, Pseudomonas aeruginosa MexAB and Staphylococcus aureus NorA efflux pumps. Int J Antimicrob Agents 33:174–176. https://doi.org/10.1016/j.ijantimicag.2008.07.032 CrossRefPubMedGoogle Scholar
- Roca I, Akova M, Baquero F, Carlet J, Cavaleri M, Coenen S, Cohen J, Findlay D, Gyssens I, Heure OE, Kahlmeter G, Kruse H, Laxminarayan R, Liébana E, López-Cerero L, MacGowan A, Martins M, Rodríguez-Baño J, Rolain JM, Segovia C, Sigauque B, Taconelli E, Wellington E, Vila J (2015) The global threat of antimicrobial resistance: science for intervention. New Microbes New Infect 6:22–29. https://doi.org/10.1016/j.nmni.2015.02.007 CrossRefPubMedPubMedCentralGoogle Scholar
- Sánchez Y, Betancur A, Agudelo M, Orduz S (2015) Peptide ID 1.0. Un programa para buscar potenciales péptidos bioactivos en secuencias de proteínas. Dirección Nacional de Derechos de Autor. Ministerio del Interior. Registro 13-50-213 del 12 de Noviembre de 2015Google Scholar
- World Health Organization (2012) The evolving threat of antimicrobial resistance: options for action 2012. ISBN 978 92 4 150318 1Google Scholar
- World Health Organization (2014) Antimicrobial resistance: global report on surveillance 2014. ISBN: 978 92 4 156474 8Google Scholar