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Biology subjects

Woolston, B. M.

Publications and source records attributed to Woolston, B. M..

2 recordsLinked to original sources

Characterization of vaginal microbial enzymes identifies amylopullulanases that support growth of Lactobacillus crispatus on glycogen

The healthy human vaginal microbiota is generally dominated by lactobacilli, and the transition to a more diverse community of anaerobic microbes is associated with health risks. Glycogen released by lysed epithelial cells is believed to be an important nutrient source in this environment. However, the mechanism by which vaginal bacteria metabolize glycogen is unclear, with evidence implicating both microbial and human enzymes. Here, we biochemically characterize six glycogen-degrading enzymes (GDEs) from vaginal bacteria that support the growth of amylase-deficient L. crispatus on glycogen. We reveal variations in the pH tolerance and susceptibility to inhibition between enzymes from different organisms. Analysis of vaginal microbiome datasets show these enzymes are expressed in all Community State Types. Finally, we confirm the presence and activity of bacterial GDEs in cervicovaginal fluid. This work establishes that bacterial GDEs can participate in the breakdown of glycogen, providing insight into metabolism that may shape the vaginal microbiota.

biochemistry↗

Cysteine dependence in Lactobacillus iners constitutes a novel therapeutic target to modify the vaginal microbiota

Vaginal microbiota composition affects several important reproductive health outcomes. Lactobacillus crispatus-dominant bacterial communities have favorable associations whereas anaerobe-dominant communities deficient of lactobacilli are linked to poor outcomes, including bacterial vaginosis (BV). Lactobacillus iners, the most abundant vaginal species worldwide, has adverse associations compared to L. crispatus, but standard metronidazole treatment for BV promotes L. iners-dominance, likely contributing to post-treatment relapse. L. iners is under-studied because it fails to grow in standard Lactobacillus media in vitro. Here we trace this in vitro phenotype to a species-specific cysteine requirement associated with limitations in cysteine-related transport mechanisms and show that vaginal cysteine concentrations correlate with Lactobacillus abundance in vivo. We demonstrate that cystine uptake inhibitors selectively impede L. iners growth and that combining an inhibitor with metronidazole thus promotes L. crispatus dominance of defined BV-like communities. These findings identify a novel target for therapeutic vaginal microbiota modulation to improve reproductive health.

microbiology↗