Jump to main content
Jump to site search


Systematic mutagenesis of oncocin reveals enhanced activity and insights into the mechanisms of antimicrobial activity

Author affiliations

Abstract

Oncocin is a proline-rich antimicrobial peptide that inhibits protein synthesis by binding to the bacterial ribosome. In this work, the antimicrobial activity of oncocin was improved by systematic peptide mutagenesis and activity evaluation. We found that a pair of cationic substitutions (P4K and L7K/R) improves the activity by 2–4 fold (p < 0.05) against multiple Gram-negative bacteria. An in vitro transcription/translation assay indicated that the increased activity was not because of stronger ribosome binding. Rather a cellular internalization assay revealed a higher internalization rate for the optimized analogs thereby suggesting a mechanism to increase potency. In addition, we found that the optimized peptides' benefit is dependent upon nutrient-depleted media conditions. The molecular design and characterization strategies have broad potential for development of antimicrobial peptides.

Graphical abstract: Systematic mutagenesis of oncocin reveals enhanced activity and insights into the mechanisms of antimicrobial activity

Back to tab navigation

Supplementary files

Publication details

The article was received on 07 Aug 2018, accepted on 05 Oct 2018 and first published on 08 Oct 2018


Article type: Paper
DOI: 10.1039/C8ME00051D
Citation: Mol. Syst. Des. Eng., 2018, Advance Article
  •   Request permissions

    Systematic mutagenesis of oncocin reveals enhanced activity and insights into the mechanisms of antimicrobial activity

    P. Lai, K. Geldart, S. Ritter, Y. N. Kaznessis and B. J. Hackel, Mol. Syst. Des. Eng., 2018, Advance Article , DOI: 10.1039/C8ME00051D

Search articles by author

Spotlight

Advertisements