Osmoprotective polymer additives attenuate the membrane pore-forming activity of antimicrobial peptoids

Peter T. Smith, Mia L. Huang, Kent Kirshenbaum

Research output: Contribution to journalArticle

Abstract

Antimicrobial peptides (AMPs) are critical components of the innate immune system and exhibit bactericidal activity against a broad spectrum of bacteria. We investigated the use of N-substituted glycine peptoid oligomers as AMP mimics with potent antimicrobial activity. The antimicrobial mechanism of action varies among different AMPs, but many of these peptides can penetrate bacterial cell membranes, causing cell lysis. We previously hypothesized that amphiphilic cyclic peptoids may act through a similar pore formation mechanism against methicillin-resistant Staphylococcus aureus (MRSA). Peptoid-induced membrane disruption is observed by scanning electron microscopy and results in a loss of membrane integrity. We demonstrate that the antimicrobial activity of the peptoids is attenuated with the addition of polyethylene glycol osmoprotectants, signifying protection from a loss of osmotic balance. This decrease in antimicrobial activity is more significant with larger osmoprotectants, indicating that peptoids form pores with initial diameters of ∼2.0-3.8 nm. The initial membrane pores formed by cyclic peptoid hexamers are comparable in diameter to those formed by larger and structurally distinct AMPs. After 24 h, the membrane pores expand to >200 nm in diameter. Together, these results indicate that cyclic peptoids exhibit a mechanism of action that includes effects manifested at the cell membrane of MRSA.

Original languageEnglish (US)
Pages (from-to)227-236
Number of pages10
JournalBiopolymers - Peptide Science Section
Volume103
Issue number4
DOIs
StatePublished - Apr 1 2015

Fingerprint

Peptoids
Polymers
Membranes
Peptides
Methicillin
Cell membranes
Methicillin-Resistant Staphylococcus aureus
N-substituted Glycines
Cell Membrane
Immune system
Oligomers
Electron Scanning Microscopy
Polyethylene glycols
Amino acids
Immune System
Bacteria
Scanning electron microscopy

Keywords

  • antimicrobial peptides
  • macrocycles
  • MRSA
  • peptidomimetics

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Biomaterials
  • Organic Chemistry

Cite this

Osmoprotective polymer additives attenuate the membrane pore-forming activity of antimicrobial peptoids. / Smith, Peter T.; Huang, Mia L.; Kirshenbaum, Kent.

In: Biopolymers - Peptide Science Section, Vol. 103, No. 4, 01.04.2015, p. 227-236.

Research output: Contribution to journalArticle

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