Virginia Via Research Day Book 2026

Faculty Research Biomedical

03 DISCOVERY OF VRE-92, A POTENT AND MICROBIOME-SPARING BACTERICIDAL AGENT TARGETING VANCOMYCIN-RESISTANT ENTEROCOCCI

Mohamed F Mohamed, PhD 1,2 ; Somaia M Abdelmegeed MSc. 1,2, Zakaria A. Elmageed, PhD, 3 ; Mohamed N Seleem, PhD 1,2 Corresponding author: mohamedm@vt.edu

1 Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, Virginia; 2 Center for One Health Research, Virginia Tech, Blacksburg, Virginia 3 Edward Via College of Osteopathic Medicine, Monroe, Louisiana.

including linezolid-resistant strains, using standard MIC and MBC assays. Cytotoxicity and hemolysis were evaluated in mammalian cell lines and human erythrocytes. In vivo efficacy was tested using a Caenorhabditis elegans VRE infection model, comparing bacterial load reduction by VRE-92 to linezolid. Microbiome-sparing effects were assessed by examining the compound's activity against representative commensal gut bacteria. Results: VRE-92 exhibited potent and selective bactericidal activity against VRE, with an MIC and MBC of 0.5 -1 µg/mL and no detectable cytotoxicity or hemolytic activity. In vivo, VRE-92 significantly reduced bacterial burden in the C. elegans VRE infection model and outperformed linezolid. VRE 92 lost its activity against beneficial gut microbiota, suggesting a microbiome-sparing profile.

Context: Vancomycin-resistant enterococci (VRE) represent a critical antimicrobial resistance threat in clinical settings, contributing to rising morbidity, mortality, and healthcare costs. Current therapies, including linezolid and daptomycin, are increasingly limited by emerging resistance, suboptimal bactericidal activity, and negative effects on the gut microbiome. Identifying new microbiome-preserving therapeutics is essential to improving treatment outcomes for multidrug-resistant VRE infections. Objective/Hypothesis: To evaluate the bactericidal activity, safety, and in vivo efficacy of VRE-92, a novel antimicrobial scaffold, and to determine whether it represents a microbiome-sparing therapeutic candidate for VRE infections. Methods: We assessed the in vitro antibacterial activity of VRE-92 against VRE clinical isolates,

Conclusions: VRE-92 is a promising therapeutic candidate with potent bactericidal activity against multidrug-resistant VRE, favorable safety characteristics, and microbiome-sparing properties. These findings support further development of VRE-92 for the treatment of VRE infections.

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116 Edward Via College of Osteopathic Medicine (VCOM)