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Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms.
- Source :
-
Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Oct 22; Vol. 63 (11). Date of Electronic Publication: 2019 Oct 22 (Print Publication: 2019). - Publication Year :
- 2019
-
Abstract
- 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.<br /> (Copyright © 2019 American Society for Microbiology.)
- Subjects :
- Animals
Candida albicans drug effects
Candidiasis drug therapy
Candidiasis microbiology
Male
Mice
Mice, Inbred BALB C
Microbial Sensitivity Tests methods
Microbial Viability drug effects
Staphylococcal Infections drug therapy
Staphylococcal Infections microbiology
Staphylococcus aureus drug effects
Anti-Infective Agents pharmacology
Biofilms drug effects
Cholic Acid pharmacology
Peptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-6596
- Volume :
- 63
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Antimicrobial agents and chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 31427303
- Full Text :
- https://doi.org/10.1128/AAC.00520-19