Investigating treponema pallidum pathobiology in the cervicovaginal niche

Dalhousie University received a $283,694 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), effective September 16, 2025, through August 31, 2027. The award funds research investigating Treponema pallidum pathobiology in the cervicovaginal niche, addressing critical gaps in understanding how the syphilis bacterium penetrates and establishes infection in female genital epithelial barriers. The research utilizes in vitro co-culture models to examine T. pallidum interactions with vaginal and endocervical epithelial tissues and to evaluate whether vaginal microbiota can modulate susceptibility to infection.

The project delivers scientific knowledge and research findings intended to identify new biomedical intervention strategies for syphilis prevention in women, with particular emphasis on evaluating probiotics or postbiotics as potential risk-reduction mechanisms. This research addresses an urgent public health need, given the 866% increase in female syphilis cases over the past decade in the United States and the concurrent 10-fold increase in congenital infections. The work supports NIAID's mission to fund investigator-initiated research that advances understanding of infectious disease mechanisms and develops innovative approaches to disease prevention and control.

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.