Gardnerella vaginalis small colony variants

项目总结

PROJECT SUMMARY Bacterial vaginosis (BV) is the most common gynecological disorder in women of childbearing age and is associated with adverse pregnancy outcomes and enhanced transmission of sexually-transmitted diseases. Gardnerella vaginalis is the signature bacterial species associated with BV, but its mechanisms of infection and persistence are not well understood. Furthermore, the mechanisms by which G. vaginalis infection recurs after antibiotic treatment are not known. We have discovered that G. vaginalis grows in two different forms, as a slow-growing small colony variant (SCV) and as a faster-growing large colony variant (LCV). The SCV form produces more of the toxin vaginolysin, is more antibiotic resistant, and is more inhibitory to the growth of Lactobacillus spp. The LCV produces more biofilms and is more inhibitory to the growth of Neisseria gonorrhoeae. Preliminary proteomic analyses indicate that SCVs downregulate DNA replication and protein synthesis and upregulate vaginolysin and other putative virulence factors. We hypothesize that the SCV is a form of the bacteria primed for initiating infection or for persisting under adverse conditions, while the LCV gives faster multiplication and builds the biofilm that supports multiple BV-associated pathogens. For these studies, we will characterize differences in infection abilities of the SCVs and make mutants to characterize the key factors involved in the increased virulence and altered metabolism of the variant form. Pathogenesis studies will include infection of human cervical tissue in organ culture. We will identify mechanisms involved in persistence and survival in adverse conditions using proteomics and measurements of antibiotic resistance, and we will identify factors stimulating phase variation.