Maggie Bui

Program: Computational and Systems Biology

Current advisor: Andrew L. Kau, MD, PhD

Undergraduate university: University of California-Los Angeles, 2020

Enrollment year: 2020

Research summary
Elucidating the fitness determinants underlying uropathogenic E. coli gut colonization

Urinary tract infections (UTIs) affect approximately 150 million people per year worldwide. Women are more susceptible to developing a UTI than men are due to anatomical differences; an estimated 50% of women report having had a UTI at some point in their lifetime, and 25% of women with a recent UTI will suffer from a recurrent UTI within six months. Antibiotic use, while the mainstay of UTI treatment, has contributed to the rise in antimicrobial resistance. Uropathogenic Escherichia coli (UPEC) is implicated in about 75% of uncomplicated UTI cases, which has led to interest in understanding the mechanisms utilized by UPEC in UTI pathogenesis. Interestingly, previous work has shown that UPEC can colonize both the bladder and gastrointestinal (GI) tract. This sets up a model for recurrent UTI in which UPEC establishes a gut reservoir from which it seeds the urinary tract. Thus, targeting UPEC in the GI tract could contribute considerably to UTI prevention.

Previous work from our lab has shown that response to oral vaccination against UPEC in the GI tract requires sufficient niche competition from other members of the gut microbiota. This competition can drive two identical UPEC strains to occupy two distinct gut compartments depending on when they were introduced: the first strain inhabits the luminal compartment, and the second strain establishes in the mucosal compartment. To investigate the fitness factors and metabolic requirements that enable this localization, we created a barcoded transposon library in UPEC strain UTI89. To validate the pooled UTI89 barcoded transposon library and identify nutritional dependencies of UPEC in different in vitro conditions, we grew UTI89 in minimal media supplemented with a different nutrient source for each condition. We also conducted an in vivo library screen using single housed, germ-free C57BL/6 mice to identify the fitness determinants necessary for UTI89 gut colonization when there is competition from a pre-existing gut microbiota, including an isogenic UTI89 strain. Through the in vitro screen, we found key genes for survival in different media conditions. Furthermore, we identified fitness genes important for mouse gut colonization. Identifying UPEC fitness determinants will elucidate the factors governing UPEC niche occupancy and inform design of antibiotic-sparing interventions for UTI.

Graduate publications