Genetic Elements Orchestrating Glycogen Metabolism in the Vagina.

Glycogen in the female lower reproductive tract is a major carbon source for colonization and acidification by common vaginal species, such as . Previously, we identified the amylopullulanase encoding gene of to correlate with the ability to autonomously utilize glycogen for growth. Here, we further characterize genetic variation and differential regulation of affecting the presence of its gene product on the outer surface layer. We show that alpha-glucan degrading activity dissipates when is grown on glucose, maltose and maltotriose, in agreement with carbon catabolite repression elements flanking the gene. Proteome analysis of the S-layer confirmed that the amylopullulanase protein is highly abundant in an S-layer enriched fraction, but not in a strain with a defective amylopullulanase variant or in an amylopullulanase-sufficient strain grown on glucose. In addition, we provide evidence that mutants are relevant in vivo, as they are commonly observed in metagenome datasets of human vaginal microbial communities. Analysis of the largest publicly available dataset of 1507 human vaginal metagenomes indicates that among the 270 samples that contain a gene, 62 samples (23%) had a defective variant of this gene. Taken together, these results demonstrate that both environmental, as well as genetic factors explain the variation of alpha-glucosidases in the vaginal environment.