Jesse Pak

Program: Molecular Microbiology and Microbial Pathogenesis

Current advisor: Juliane Bubeck Wardenburg, MD, PhD

Undergraduate university: Pepperdine University-Malibu, 2020

Enrollment year: 2022

Research summary
Investigating the role of a novel B. fragilis toxin in interbacterial competition and niche acquisition

Bacteroides fragilis is an opportunistic pathogen that can be found in the human intestinal microbiome within the first month of life. In the context of a neonatal evolving community, competition is established for the acquisition of nutrients and space, as well as for long-term gut colonization. The Type 6 Secretion System (T6SS) of B. fragilis is ubiquitous throughout the species and has been shown to play a key role in interbacterial competition. However, in a representative strain from a unique clade of B. fragilis that harbors carbapenem resistance (clade II), we observed activity of unknown competitive factor(s) that were independent of T6SS. Through a forward genetic screen, we defined a novel B. fragilis toxin, Bcf1, as a 56 kDa secreted protein that enables a competitive advantage against B. fragilis strains from the opposing clade I. A bcf1 isogenic deletion mutant demonstrated impaired competition in vitro, and upon addition of purified Bcf1, the competitive phenotype was restored. Within the adjacent genetic locus, we also identified Bat1, a functional target of Bcf1, which is a putative TonB-dependent transporter implicated in nutrient uptake. We propose that Bcf1 interacts with Bat1 from an opposing clade strain, limiting nutrient availability and conferring a competitive advantage for the Bcf1-secreting strain. This work reveals a novel molecular interaction within the antagonistic arsenal of B. fragilis and broadens our mechanistic understanding of factors that provide a competitive advantage within the colonic niche which may contribute to a reservoir for carbapenem resistance in humans.

Graduate publications