Sequence permutation generates peptides with different antimicrobial and antibiofilm activities

Biswajit Mishra, Jayaram Lakshmaiah Narayana, Tamara Lushnikova, Yingxia Zhang, Radha M. Golla, D. Zarena, Guangshun Wang

Research output: Contribution to journalArticle

Abstract

Antibiotic resistance poses a threat to our society, and 10 million people could die by 2050. To design potent antimicrobials, we made use of the antimicrobial peptide database (APD). Using the database filtering technology, we identified a useful template and converted it into an effective peptide WW291 against methicillin-resistant Staphylococcus aureus (MRSA). Here, we compared the antibacterial activity and cytotoxicity of a family of peptides obtained from sequence permutation of WW291. The resulting eight WW peptides (WW291-WW298) gained different activities against a panel of bacteria. While WW295 inhibited the growth of Escherichia coli, WW298 was highly active against S. aureus USA300 LAC. Consistently with this, WW298 was more effective in permeating or depolarizing the S. aureus membranes, whereas WW295 potently permeated the E. coli membranes. In addition, WW298, but not WW295, inhibited the MRSA attachment and could disrupt its preformed biofilms more effectively than daptomycin. WW298 also protected wax moths Galleria mellonella from MRSA infection causing death. Thus, sequence permutation provides one useful avenue to generating antimicrobial peptides with varying activity spectra. Taken together with amino acid composition modulation, these methods may lead to narrow-spectrum peptides that are more promising to selectively eliminate invading pathogens without damaging commensal microbiota.

Original languageEnglish (US)
Article number271
Pages (from-to)1-18
Number of pages18
JournalPharmaceuticals
Volume13
Issue number10
DOIs
StatePublished - Oct 2020

Keywords

  • Antibiotic resistance
  • Antimicrobial peptides
  • Database
  • Peptide discovery
  • Sequence permutation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science

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  • Cite this

    Mishra, B., Narayana, J. L., Lushnikova, T., Zhang, Y., Golla, R. M., Zarena, D., & Wang, G. (2020). Sequence permutation generates peptides with different antimicrobial and antibiofilm activities. Pharmaceuticals, 13(10), 1-18. [271]. https://doi.org/10.3390/ph13100271