Virginia Research Day 2025

Graduate Student Research Biomedical

03 Evaluation of Novel Synthetic Antimicrobial Peptides Against Vancomyci-Resistant Enterococci (VRE)

Abdelmegeed S. 1,2 ; Mohamed M. 1,2 ; Abouelkhair A.A. 1,2 ; Abutaleb N.S. 1,2 ; Abdelsattar A. 1,2 ; Seleem M 1,2 Corresponding author: somaiamahmoud@vt.ed

1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 2 Center for One Health Research, Virginia Tech, Blacksburg, Virginia

Vancomycin-resistant Enterococci (VRE) present a significant challenge in clinical settings due to their resistance to conventional antibiotics. This study explores the antimicrobial efficacy of newly designed derivatives of a short αhelical peptide, RR. Among the variants, RR4 and its D-enantiomer, D-RR4, exhibited over a 32-fold enhancement in antimicrobial activity

against multi-drug resistant VRE strains. Notably, D-RR4 demonstrated superior biofilm disruption compared to traditional antibiotics. Mechanistic investigations revealed that these peptides depolarize and permeabilize bacterial membranes, leading to the leakage of intracellular contents. Additionally, the peptides displayed rapid bactericidal action.

Similar to linezolid, D-RR4 demonstrated 100% survival of infected mice in a VRE peritonitis model. Interestingly, D-RR4 caused significant reduction of bacteria inside kidney and spleen compared to both untreated and linezolid. These results highlight D-RR4 as a promising therapeutic option in combating VRE infections.

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