Improving the Activity and Selectivity of a Scorpion-Derived Peptide, A3a, against <i>Acinetobacter baumannii</i> through Rational Design.

ABSTRACT: The rise in antimicrobial resistance has led to an increased desire to understand how antimicrobial peptides (AMPs) can be better engineered to kill antibiotic-resistant bacteria. Previously, we showed that C-terminal amidation of a peptide, identified in scorpion Androctonus amoreuxi venom, increased its activity against both Gram-positive and -negative bacteria. Here, we incorporate all-atom molecular dynamics (MD) simulations in a rational design strategy to create analogues of A3a with greater therapeutic potential. We discover two novel AMPs which achieve greater potency against, and selectivity toward, Acinetobacter baumannii ATCC 19606 but via two distinct mechanisms and which are effective in Galleria mellonella models of A. baumannii burn wound infectio

SUBMITTER: Moller DS 

PROVIDER: S-EPMC11822712 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature