Project description:Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.
Project description:Lactobacilli have long been regarded as important constituents of the healthy human vagina. Lactobacillus iners is the most frequently detected bacterial species in the vagina, but little is known about its characteristics. We report a description of the whole-genome sequence of L. iners AB-1 along with comparative analysis of published genomes of closely related strains of lactobacilli. The genome is the smallest Lactobacillus reported to date, with a 1.3-Mbp single chromosome. The genome seems to have undergone one or more rapid evolution events that resulted in large-scale gene loss and horizontal acquisition of a number of genes for survival in the vagina. L. iners may exhibit specialized adaptation mechanisms to the vaginal environment, such as an iron-sulfur cluster assembly system, and several unique ? factors to regulate gene transcription in this fluctuating environment. A potentially highly expressed homolog of a cholesterol-binding lysin may also contribute to host cell adhesion or act as a defense mechanism against other microbes. Notably, there is a lack of apparent adhesion proteins, but several cell-anchor proteins were identified and may be important for interaction with the host mucosal tissues. L. iners is widely present in healthy females as well as those suffering from bacterial vaginosis or who have undergone antimicrobial therapy, suggesting that it is an important indigenous species of the vagina.