Enterocin A mutants identified by saturation mutagenesis enhance potency towards vancomycin-resistant Enterococci

Maria K. Mcclintock, Yiannis N. Kaznessis, Benjamin J. Hackel

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Vancomycin-resistant Enterococci infections are a significant clinical problem. One proposed solution is to use probiotics, such as lactic acid bacteria, to produce antimicrobial peptides at the site of infection. Enterocin A, a class 2a bacteriocin, exhibits inhibitory activity against E. faecium and E. faecalis, which account for 86% of vancomycin-resistant Enterococci infections. In this study, we aimed to engineer enterocin A mutants with enhanced potency within a lactic acid bacterial production system. Peptide mutants resulting from saturation mutagenesis at sites A24 and T27 were efficiently screened in a 96-well plate assay for inhibition of pathogen growth. Several mutants exhibit increased potency relative to wild-type enterocin A in both liquid- and solid-medium growth assays. In particular, A24P and T27G exhibit enhanced inhibition of multiple strains of E. faecium and E. faecalis, including clinically isolated vancomycin-resistant strains. A24P and T27G enhance killing of E. faecium 8 by 13±3- and 18±4-fold, respectively. The engineered enterocin A/lactic acid bacteria systems offer significant potential to combat antibiotic-resistant infections.

Original languageEnglish (US)
Pages (from-to)414-423
Number of pages10
JournalBiotechnology and bioengineering
Volume113
Issue number2
DOIs
StatePublished - Feb 1 2016

Keywords

  • Antimicrobial peptide
  • Enterocin A
  • Lactic acid bacteria
  • Peptide engineering
  • Saturation mutagenesis

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