Sarah Grambo

Program: Molecular Microbiology and Microbial Pathogenesis

Current advisor: Megan T. Baldridge, MD, PhD

Undergraduate university: Iowa State University, 2021

Enrollment year: 2022

Research summary
Investigating the contribution of bacteriophages to inflammation during dysbiosis in the female genital tract and human enteric system.

Inflammatory conditions of mucosal surfaces account for many serious and widespread diseases in humans. Bacterial vaginosis (BV) is an inflammatory condition of the female genital tract (FGT) that correlates with a shift in the vaginal microbiota from a Lactobacillus-dominated community to a diverse, often anaerobe-populated community. BV is the number one reason that women seek gynecological care appointments in the US, and around 30% of women will experience this condition at least once. BV significantly increases the risk of acquiring STDs, including HIV, and passing STDs to sexual partners.
Studies of inflammatory conditions in other mucosal body sites, such as inflammatory bowel disease in the human gut, have supported a role for bacteriophages (phages) in shifting microbial communities towards dysbiotic states. Phage population richness often parallels their host bacteria richness, but due to the ability to infect multiple bacterial species and to lysogenize then burst as a population, phages create distinct communities from their bacterial hosts and are hypothesized to shift their mucosal compartments from healthy to inflammatory. The FGT phageome has only been characterized at a basic level and its role in dysbiosis via interaction with bacterial hosts is unclear. The phageome may also contribute directly to inflammation by inducing an inflammatory type I interferon response. To answer fundamental questions about the role of phage in the human body and improve treatment of BV, it is necessary to understand the direct and indirect effects of phages on the human host during dysbiosis. I hypothesize that phages cause inflammation during dysbiosis via modifications to the microbiota and direct interactions with the human host. My project has two major approaches. First, determine the effects of phages on the human host through direct adherence of phages to human cells. Second, characterize the effects of phage on dysbiosis through phage-bacterial host interactions and indirect human host effects. Work on this project will yield improved understanding of phage contributions to inflammation through interactions with bacteria and direct interactions.

Graduate publications