Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms.

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.

• Authors: Siddhi Gupta, Jyoti Thakur, Sanjay Pal, Ragini Gupta, Deepakkumar Mishra, Sandeep Kumar, Kavita Yadav, Amandeep Saini, Prabhu S Yavvari, Madhukar Vedantham, Archana Singh, Aasheesh Srivastava, Rajendra Prasad, Avinash Bajaj
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 63 Issue 11 (11 2019) ISSN: 1098-6596 [Electronic] United States
• PMID: 31427303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Microbiology.

Chemical References

• Anti-Infective Agents
• Peptides
• Cholic Acid

Topics

• Animals
• Anti-Infective Agents (pharmacology)
• Biofilms (drug effects)
• Candida albicans (drug effects)
• Candidiasis (drug therapy, microbiology)
• Cholic Acid (pharmacology)
• Male
• Mice
• Mice, Inbred BALB C
• Microbial Sensitivity Tests (methods)
• Microbial Viability (drug effects)
• Peptides (pharmacology)
• Staphylococcal Infections (drug therapy, microbiology)
• Staphylococcus aureus (drug effects)