Wyman Chan

Program: Master’s Program in Cell and Molecular Biology
Date: Wednesday, May 13, 2026
Time: 11:00am
Location: Donald P. Shiley BioScience Center (BSCI)
Zoom: https://SDSU.zoom.us/j/9508918377

Committee Members

Dr. Zayas, Biology
Dr. Angelica Riestra, Biology
Dr. Tom Huxford, Chemistry
Dr. Dwayne Roach, Biology

Abstract

Tuberculosis remains a leading cause of infectious disease mortality worldwide, necessitating alternative therapeutic strategies capable of targeting Mycobacterium tuberculosis within complex host environments. This need is driven by the prolonged treatment regimens, poor patient adherence, and the increasing emergence of multidrug-resistant and extensively drug-resistant strains that compromise the efficacy of conventional antibiotic therapies. Bacteriophages represent a promising yet underdeveloped therapeutic approach for mycobacterial infections; however, translational advancement requires evaluation beyond environmental recovery and lytic activity.

This study establishes a multi-scale framework for therapeutic mycobacteriophage characterization, progressing from environmental isolation to structured biofilm and intracellular infection models. Two phages, PHG-Myc4 and PHG-Myc5, were isolated from the environment with the capability to infect M. tuberculosis. Comparative genomic analysis positioned Myc4 within established mycobacteriophage cluster AB, and benchmarked Myc4 against Muddy, a clinically applied phage. Genomic comparison between these two phages revealed a high conservation in most gene functions with deviations in key genes, altering infection dynamics. Two novel assays were developed to accurately evaluate Myc4 and Myc5’s potential as therapeutics by testing them in physiologically relevant models.

When evaluated against biofilm populations using a microfluidic platform, Myc4 and Myc5 were able to suppress the structured biomass, while each exhibiting unique diffusion patterns. Furthermore, although reductions in intracellular bacterial burden were modest, both phages still demonstrated the capacity for intracellular persistence—providing the initial evidence that phages retain activity within infected host cells. Collectively, these findings position phages such as Myc4 as promising candidates for suppressing M. tuberculosis infection based on its consistent performance across different restrictive biological niches.