The purpose of this notice of funding opportunity (NOFO) is to support basic and exploratory research projects to advance our understanding of T. pallidum bacterial pathogenesis. Centers for Disease Control (CDC) national surveillance data has shown rates of Sexually Transmitted Infections (STIs) surging for the seventh straight year, including syphilis, which has had an 80% increase in cases since 2017. There were 3,700 congenital syphilis cases reported in 2022, a 937% increase in the past decade. Concurrently, there is a periodic global shortage of benzathine penicillin G, the first line treatment for syphilis. Historically, there have been significant scientific barriers for laboratories to initiate syphilis basic research, including the requirement to propagate the causative bacterial agent, Treponema pallidum, in rabbits, an expensive and complex animal model, and a lack of genetic tools for bacterial pathogenesis studies. Recent significant scientific advances in T. pallidum in vitro culture, transformation and targeted mutagenesis technology, and the availability of reagents for use in the guinea pig model of congenital syphilis lowers these historic barriers and may facilitate the entrance of new investigators into the field of syphilis research.