Jesse Pak
Program: Molecular Microbiology and Microbial Pathogenesis
Current advisor: Juliane Bubeck Wardenburg, MD, PhD
Undergraduate university: Pepperdine University-Malibu
Research summary
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