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Efficacy of Cathelicidin-Mimetic Antimicrobial Peptoids against Staphylococcus aureus

Journal Article · · Microbiology Spectrum
 [1];  [2];  [3];  [4];  [1];  [1];  [5];  [3];  [4];  [3];  [1]
  1. Texas A&M Health Science Center, College Station, TX (United States)
  2. Texas A&M Health Science Center, College Station, TX (United States); Univ. of Edinburgh, Scotland (United Kingdom)
  3. Stanford University School of Medicine, Stanford, CA (United States)
  4. Michigan State Univ., East Lansing, MI (United States)
  5. Stanford University School of Medicine, Stanford, CA (United States); University of Roskilde (Denmark)
+ Show Author Affiliations

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 μM. 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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). Molecular Foundry
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Novo Nordisk Foundation
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1982991
Journal Information:
Microbiology Spectrum, Journal Name: Microbiology Spectrum Journal Issue: 3 Vol. 10; ISSN 2165-0497
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Antimicrobial peptides
Chemical synthesis
Microbiology
Staphylococcus aureus