Investigating Treponema pallidum pathobiology in the cervicovaginal niche

ABSTRACT: Globally, infectious and congenital syphilis cases continue to increase at alarming rates. In the United States, syphilis infection rates remain highest among men, but cases in women are disproportionately accelerating, showing an 866% increase over the past decade concurrent with a 10-fold increase in congenital infections. The highly invasive syphilis bacterium, Treponema pallidum, is acquired during contact between an infectious lesion and mucosal sites, such as the lower female genital tract (vagina and cervix). From the initial infection site, treponemes enter the bloodstream and undergo systemic dissemination. However, the molecular events preceding vascular dissemination that support T. pallidum penetration of cervicovaginal epithelium have yet to be investigated. This research proposal aims to address this important gap in knowledge by investigating (1) how T. pallidum interacts with vaginal and endocervical epithelial barriers to mediate adhesion and barrier traversal and (2) whether vaginal microbiota can inhibit or augment T. pallidum interactions with cervicovaginal epithelial barriers. This work will use in vitro co-culture models to advance our understanding of how T. pallidum establishes infections in the cervicovaginal niche and whether the vaginal microbiome represents a modifiable risk factor for modulating susceptibility to T. pallidum infection. This work is expected to identify new avenues for biomedical intervention amenable for use in females, such as probiotics or postbiotics that could reduce the risk of acquiring syphilis, with the ultimate goal of diminishing the burden of infectious and congenital syphilis cases.