Efficacy of cathelicidin-mimetic antimicrobial peptoids against staphylococcus aureus

Aaron B. Benjamin, Madeleine G. Moule, Maruti K. Didwania, Jonathan Hardy, Panatda Saenkham-Huntsinger, Preeti Sule, Josefine Eilsø Nielsen, Jennifer S. Lin, Christopher H. Contag, Annelise E. Barron, Jeffrey D. Cirillo

Research output: Contribution to journalArticlepeer-review

Abstract

Staphylococcus aureus is one of the most common pathogens associated with infection in wounds. The current standard of care uses a combination of disinfection and drainage followed by conventional antibiotics such as methicillin. Methicillin and vancomycin resistance has rendered these treatments ineffective, often causing the reemergence of infection. This study examines the use of antimicrobial peptoids (sequence-specific poly-N-substituted glycines) designed to mimic naturally occurring cationic, amphipathic host defense peptides, as an alternative to conventional antibiotics. These peptoids also show efficient and fast (,30 min) killing of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) at low micromolar concentrations without having apparent cytotoxic side effects in vivo. Additionally, these novel peptoids show excellent efficacy against biofilm formation and detachment for both MSSA and MRSA. In comparison, conventional antibiotics were unable to detach or prevent formation of biofilms. One cationic 12mer, Peptoid 1, shows great promise, as it could prevent formation of and detach biofilms at concentrations as low as 1.6 mM. The use of a bioluminescent S. aureus murine incision wound model demonstrated clearance of infection in peptoid-treated mice within 8 days, conveying another advantage these peptoids have over conventional antibiotics. These results provide clear evidence of the potential for antimicrobial peptoids for the treatment of S. aureus wound infections. IMPORTANCE Staphylococcus aureus resistance is a consistent problem with a large impact on the health care system. Infections with resistant S. aureus can cause serious adverse effects and can result in death. These antimicrobial peptoids show efficient killing of bacteria both as a biofilm and as free bacteria, often doing so in less than 30 min. As such, these antimicrobials have the potential to alleviate the burden that Staphylococcus infections have on the health care system and cause better outcomes for infected patients.

Original languageEnglish
Pages (from-to)e0053422
Number of pages15
JournalMicrobiology Spectrum
Volume10
Issue number3
DOIs
Publication statusPublished - 25 Apr 2022

Keywords

  • staphylococcus aureus
  • antimicrobial peptides
  • chemical synthesis

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