Efficacy of Cathelicidin-Mimetic Antimicrobial Peptoids against Staphylococcus aureus
[1];
[4];
[1]
- Texas A&M Health Science Center, College Station, TX (United States)
- Texas A&M Health Science Center, College Station, TX (United States); Univ. of Edinburgh, Scotland (United Kingdom)
- Stanford University School of Medicine, Stanford, CA (United States)
- Michigan State Univ., East Lansing, MI (United States)
- Stanford University School of Medicine, Stanford, CA (United States); University of Roskilde (Denmark)
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; 1DP1 OD029517-01; NNF21OC0068675
- OSTI ID:
- 1982991
- Journal Information:
- Microbiology Spectrum, Vol. 10, Issue 3; ISSN 2165-0497
- Publisher:
- American Society for MicrobiologyCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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