Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 63, Issue 11, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00520-19
Keywords
antibacterial; antifungal; antimicrobials; bile acids; biofilms; membrane targeting
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Funding
- Regional Centre for Biotechnology, Amity University, Haryana
- DBT [BT/PR12297/MED/29/895/2014, BT/PR17525/MED/29/1021/2016, BT/PR27264/Med/29/1277/2018, BT/PR5480/INF/22/158/2012]
- RCB-Young investigator program
- UGC
- RCB
- Department of Biotechnology, Government of India
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Interkingdom polymicrobial biofilms formed by Gram-positive Staphylococcus aureus and Candida albicans pose serious threats of chronic systemic infections due to the absence of any common therapeutic target for their elimination. Herein, we present the structure-activity relationship (SAR) of membrane-targeting cholic acid-peptide conjugates (CAPs) against Gram-positive bacterial and fungal strains. Structure-activity investigations validated by mechanistic studies revealed that valine-glycine dipeptide-derived CAP 3 was the most effective broad-spectrum antimicrobial against S. aureus and C. albicans. CAP 3 was able to degrade the preformed single-species and polymicrobial biofilms formed by S. aureus and C. albicans, and CAP 3-coated materials prevented the formation of biofilms. Murine wound and catheter infection models further confirmed the equally potent bactericidal and fungicidal effect of CAP 3 against bacterial, fungal, and polymicrobial infections. Taken together, these results demonstrate that CAPs, as potential broad-spectrum antimicrobials, can effectively clear the frequently encountered polymicrobial infections and can be fine-tuned further for future applications.
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