Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Department of Chemical Engineering, Northeastern University, Boston, MA, USA.
Nat Microbiol. 2023 Sep;8(9):1641-1652. doi: 10.1038/s41564-023-01447-2. Epub 2023 Aug 10.
The human vaginal microbiota is frequently dominated by lactobacilli and 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 the vagina. However, the mechanism by which vaginal bacteria metabolize glycogen is unclear, with evidence implicating both bacterial and human enzymes. Here we biochemically characterize six glycogen-degrading enzymes (GDEs), all of which are pullanases (PulA homologues), from vaginal bacteria that support the growth of amylase-deficient Lactobacillus crispatus on glycogen. We reveal variations in their pH tolerance, substrate preferences, breakdown products and susceptibility to inhibition. Analysis of vaginal microbiome datasets shows that these enzymes are expressed in all community state types. Finally, we confirm the presence and activity of bacterial and human 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.
人类阴道微生物群通常以乳杆菌为主，向更具多样性的厌氧微生物群落的转变与健康风险相关。裂解的上皮细胞释放的糖原被认为是阴道中的一种重要营养源。然而，阴道细菌代谢糖原的机制尚不清楚，有证据表明涉及细菌和人类酶。在这里，我们从阴道细菌中生化表征了六种糖原降解酶（GDE），它们都是 pullanases（PullA 同源物），能够支持缺乏淀粉酶的嗜酸乳杆菌在糖原上生长。我们揭示了它们在 pH 耐受性、底物偏好、分解产物和抑制敏感性方面的差异。对阴道微生物组数据集的分析表明，这些酶在所有社区状态类型中都有表达。最后，我们在宫颈阴道分泌物中证实了细菌和人类 GDE 的存在和活性。这项工作确立了细菌 GDE 可以参与糖原的分解，为可能塑造阴道微生物群的代谢提供了深入了解。
