PROJECT SUMMARY: Sneathia vaginalis (Sv) is emerging as a pathogen that is significantly associated with preterm birth and can cause numerous infections including amnionitis, osteoarthritis, meningitis, bacteremia, and urethritis. Due to its fastidious nature, it has only recently been recognized as a pathogen through the use of DNA-based methods. Because it has been under-recognized as a pathogen, the biology and the pathogenesis of S. vaginalis remain almost entirely uncharacterized. We have identified a hemolytic and cytopathogenic toxin produced by S. vaginalis that we have named CptA. Antiserum against CptA abrogates traversal of Sv across intact human fetal membranes suggesting that the toxin plays a role in pathogenesis. This project has three main goals. The first is to assess the maternal and fetal antibody response to CptA during natural colonization/infection. The second is to establish the role of CptA in traversal of and damage to fetal membranes by Sv. The third is to determine whether the association between Sv and preterm birth is causal by developing a mouse model of Sv infection during pregnancy. pathogenesis Characterization of this novel pore-forming toxin will break ground in our understanding of this emerging pathogen.