Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 14, Issue 22, Pages 25025-25041Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.1c23734
Keywords
antibiotic; nanoengineered peptide polymer; Gram-positive; Staphylococcus aureus; antimicrobial resistance; membrane active
Funding
- National Health and Medical Research Council (NHMRC) of Australia
- Australian Research Council (ARC)
- NHMRC [APP1142472, APP1158841, APP1185426]
- ARC [DP210102781, DP160101312, LE200100163]
- Cancer Council Victoria [APP1163284]
- Centre for Oral Health Research at The Melbourne Dental School
- Australian Research Council [LE200100163] Funding Source: Australian Research Council
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Antibiotic resistance in Gram-positive bacteria is becoming a global health crisis, and the lack of new antibiotics necessitates the development of novel antimicrobial materials. The study demonstrates the preferential targeting and killing of Gram-positive pathogens by star-peptide polymers, with the eight-armed structure exhibiting the highest bactericidal activity.
Antibiotic resistance in bacteria, especially Gram-positive bacteria like Staphylococcus aureus, is gaining considerable momentum worldwide and unless checked will pose a global health crisis. With few new antibiotics coming on the market, there is a need for novel antimicrobial materials that target and kill multi-drug-resistant (MDR) Gram-positive pathogens like methicillin-resistant Staphylococcus aureus (MRSA). In this study, using a novel mixed-bacteria antimicrobial assay, we show that the star-peptide polymers preferentially target and kill Gram-positive pathogens including MRSA. A major effect on the activity of the star-peptide polymer was structure, with an eight-armed structure inducing the greatest bactericidal activity. The different star-peptide polymer structures were found to induce different mechanisms of bacterial death both in vitro and in vivo. These results highlight the potential utility of peptide/polymers to fabricate materials for therapeutic development against MDR Gram-positive bacterial infections.
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