Beyond Antibiotics: Innovations in Phage-Derived Endolysin Research
Dr. Daniel Nelson
Professor, Institute for Bioscience & Biotechnology Research, University of MarylandFebruary 26, 2025

Seminar Details
Host: BGA (Amelia Brave)
Time: 4:00-5:00pm
Location: BICH Rm 108
Seminar Abstract
Antimicrobial resistance has become a critical global health challenge, necessitating innovative therapeutic strategies beyond traditional antibiotics. This presentation explores bacteriophage-derived endolysins (cell wall hydrolases) as specific and potent antibacterial agents. Endolysins derived from bacteriophage that infect Gram-positive hosts are modular enzymes composed of enzymatically active domains (EADs) and cell wall binding domains (CBDs), which confer species specificity and high efficacy. The first section provides an overview of their structure and function, emphasizing their precision in combating bacterial pathogens. In vivo studies demonstrate their effectiveness in animal models, displaying a lower likelihood of resistance compared to traditional antibiotics. Furthermore, advancements in bioengineering, including the creation of chimeric endolysins, highlight opportunities for therapeutic optimization. The second section addresses the challenge of intracellular pathogens, focusing on PlyC, an endolysin uniquely capable of binding phosphatidylserine to cross eukaryotic membranes. This ability enables PlyC to co-localize with and eliminate intracellular streptococci, offering new avenues for tackling infections that evade conventional treatments. Finally, the presentation explores the use of endolysin CBDs to engineer Infection Site Targeted Antibodies (ISTAbs) for Bacillus anthracis. These immunotherapeutics combine toxin neutralization with effector functions. This exploration underscores the transformative potential of endolysins as next-generation antimicrobials.