TY - JOUR
T1 - Efficacy of cathelicidin-mimetic antimicrobial peptoids against staphylococcus aureus
AU - Benjamin, Aaron B.
AU - Moule, Madeleine G.
AU - Didwania, Maruti K.
AU - Hardy, Jonathan
AU - Saenkham-Huntsinger, Panatda
AU - Sule, Preeti
AU - Nielsen, Josefine Eilsø
AU - Lin, Jennifer S.
AU - Contag, Christopher H.
AU - Barron, Annelise E.
AU - Cirillo, Jeffrey D.
N1 - Funding Information:
A.E.B., J.S.L., and J.E.N. acknowledge funding from the U.S. Public Health Services (an NIH Pioneer Award to Annelise E. Barron, NIH/NIA grant number 1DP1 OD029517-01). J.E.N. was also funded by grant NNF21OC0068675 from the Novo Nordisk Foundation and the Stanford Bio-X Program. Work at the Molecular Foundry was supported by the Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. A.E.B. and J.S.L. gratefully acknowledge Michael Connolly at the Molecular Foundry for his assistance with peptoid synthesis and sample preparation equipment.
Publisher Copyright:
Copyright © 2022 Benjamin et al.
PY - 2022/4/25
Y1 - 2022/4/25
N2 - 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.
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.
AB - 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.
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.
KW - staphylococcus aureus
KW - antimicrobial peptides
KW - chemical synthesis
U2 - 10.1128/spectrum.00534-22
DO - 10.1128/spectrum.00534-22
M3 - Article
C2 - 35467395
VL - 10
SP - e0053422
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 3
ER -