Activity and selectivity of histidine-containing lytic peptides to antibiotic-resistant bacteria

Riddhi Kharidia, Zhigang Tu, Long Chen, Jun F. Liang

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Lytic peptides are a group of membrane-acting peptides that are active to antibiotic-resistant bacteria but demonstrate high toxicity to tissue cells. Here, we reported the construction of new lytic peptide derivatives through the replacement of corresponding lysine/arginine residues in lytic peptide templates with histidines. Resulting lytic peptides had the same lethality to antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus, but showed greatly improved selectivity to bacteria. When incubated with co-cultured bacteria and tissue cells, these histidine-containing lytic peptide derivatives killed bacteria selectively but spared co-cultured human cells. Membrane insertion and peptide-quenching studies revealed that histidine protonation controlled peptide interactions with cell membranes determined the bacterial selectivity of lytic peptide derivatives. Compared with parent peptides, lytic peptide derivatives bound to bacteria strongly and inserted deeply into the bacterial cell membrane. Therefore, histidine- containing lytic peptides represent a new group of antimicrobial peptides for bacterial infections in which the antibiotic resistance has developed.

Original languageEnglish
Pages (from-to)769-778
Number of pages10
JournalArchives of Microbiology
Volume194
Issue number9
DOIs
StatePublished - Sep 2012

Keywords

  • Antibiotic resistance
  • Antimicrobial peptides
  • Lytic activity
  • MRSA
  • Selectivity

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