Bajaj, Avinash and Gupta, Siddhi and Thakur, Jyoti and Pal, Sanjay and Gupta, Ragini and Mishra, Deepakkumar and Kumar, Sandeep and Yadav, Kavita and Saini, Amandeep and Yavvari, Prabhu S. and Vedantham, Madhukar and Singh, Archana and Srivastava, Aasheesh and Prasad, Rajendra (2019) Cholic Acid-Peptide Conjugates as Potent Antimicrobials against Interkingdom Polymicrobial Biofilms. Antimicrobial Agents and Chemotherapy, 63 (11). ISSN 0066-4804

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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.

Item Type:	Article
Subjects:	Biomedical Science Bioengineering & Devices
Depositing User:	RCB Library
Date Deposited:	25 Jun 2020 07:04
Last Modified:	25 Jun 2020 07:04
URI:	http://rcb.sciencecentral.in/id/eprint/268

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