Influence of the Cervicovaginal Phageome on Health and Disease in Women Living with HIV.

PROJECT SUMMARY/ABSTRACT The female reproductive tract (FRT) microbiome consists of all microbes within that space, including the bacteriome and the virome, which is comprised of the phageome (bacteriophages) and eukaryotic viruses. Low diversity Lactobacillus-dominant bacteriomes play a pivotal protective role in maintaining women’s health, including preventing pre-term birth, bacterial vaginosis (BV), yeast infections, and sexually transmitted infections. However, shifts to high diversity FRT bacteriomes, such as in BV, result in increased FRT inflammation, and consequent increased risk of symptomatic BV, pre-term birth, and STIs including HIV. Bacteriophages are natural predators of bacteria and are more numerous and diverse than bacteria and may serve to regulate bacterial populations. Our prior work showed the FRT bacteriophages form communities which corresponded with FRT diseases; however, the mechanisms behind bacteriophage contribution to regulating FRT bacterial populations is largely undetermined. Our main objective is to determine the how these phageome communities contribute to FRT health by regulating alterations in the bacteriome. In this proposal, we will utilize metagenomic sequencing on FRT samples from a unique longitudinal cohort comprised of US women living with HIV and AIDS compared to healthy controls to investigate (Aim 1) the FRT phageome communities over time, (Aim 2) the impact of AIDS and antiretroviral therapy on the phageome, and (Aim 3) identify predictive taxonomic and metagenomic biomarkers of shifts to high diversity FRT bacteriomes using bioinformatic knowledge gained during my career development plan. My long-term career goal is to become an independently funded physician scientist leading a translational research team to elucidate the virome’s influence on human health and disease and to develop novel strategies to mitigate disease. My career development plan lays out a detailed strategy to augment my expertise in computational biology and microbiome biostatistics, with the overall goal to improve my viral and bacterial metagenomic pipelines, including functional annotation. An improved understanding of bacteriophage- bacterial interactions in the FRT including biomarkers predictive of pathogenic FRT shifts, will pave the way toward novel preventative strategies and phage-based therapeutics for FRT diseases including BV and STIs, thereby improving women’s reproductive health.