Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides

Margarita Karapetian; Evgenia Alimbarashvili; Boris Vishnepolsky; Andrei Gabrielian; Alex Rosenthal; Darrell E Hurt; Michael Tartakovsky; Mariam Mchedlishvili; Davit Arsenadze; Malak Pirtskhalava; Giorgi Zaalishvili

doi:10.1016/j.heliyon.2024.e27852

Evaluation of the synergistic potential and mechanisms of action for de novo designed cationic antimicrobial peptides

Heliyon. 2024 Mar 13;10(6):e27852. doi: 10.1016/j.heliyon.2024.e27852. eCollection 2024 Mar 30.

Affiliations

¹ Laboratory of Chromatin Biology, Institute of Cellular and Molecular Biology, Agricultural University of Georgia, 240 David Aghmashenebeli Alley, 0159, Tbilisi, Georgia.
² Ivane Beritashvili Center of Experimental Biomedicine, 0160, Tbilisi, Georgia.
³ Oﬃce of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.

Abstract

Antimicrobial peptides (AMPs) have emerged as promising candidates in combating antimicrobial resistance - a growing issue in healthcare. However, to develop AMPs into effective therapeutics, a thorough analysis and extensive investigations are essential. In this study, we employed an in silico approach to design cationic AMPs de novo, followed by their experimental testing. The antibacterial potential of de novo designed cationic AMPs, along with their synergistic properties in combination with conventional antibiotics was examined. Furthermore, the effects of bacterial inoculum density and metabolic state on the antibacterial activity of AMPs were evaluated. Finally, the impact of several potent AMPs on E. coli cell envelope and genomic DNA integrity was determined. Collectively, this comprehensive analysis provides insights into the unique characteristics of cationic AMPs.

Keywords: AMP; CAMP; E. coli; Synergy.