Abstract
Porphyromonas asaccharolytica and Porphyromonas uenonis are common inhabitants of the vaginal microbiome, but their presence has been linked to adverse health outcomes for women, including bacterial vaginosis and preterm birth. However, little is known about the pathogenesis mechanisms of these bacteria. The related oral opportunistic pathogen, Porphyromonas gingivalis, is comparatively well-studied and known to secrete numerous extracellular matrix-targeting proteases. Among these are the gingipain family of cysteine proteases that drive periodontal disease progression and hematogenic transmission to the placenta. In this study, we demonstrate that vaginal Porphyromonas species secrete broad-acting proteases capable of freely diffusing within the cervicovaginal niche. These proteases degrade collagens that are enriched within the cervix (type I) and chorioamniotic membranes (type IV), as well as fibrinogen, which inhibits clot formation. Bioinformatic queries confirmed the absence of gingipain orthologs and identified five serine, cysteine, and metalloprotease candidates in each species. Inhibition assays revealed that each species’ proteolytic activity can be partially attributed to a secreted metalloprotease with broad substrate specificity that is distantly related to the P. gingivalis endopeptidase PepO. This characterization of virulence activities in vaginal Porphyromonas species highlights their potential to alter the homeostasis of reproductive tissues and harm human pregnancy through clotting disruption, fetal membrane weakening, and premature cervical remodeling.
Highlights
The vaginal microbiome of healthy reproductive-age women is typically characterized by low species diversity, with Lactobacillus dominating the vaginal and ectocervical niches of the lower genital tract[1,2]
Tertiary structure, casein is regarded as a universal protease we show that P. asaccharolytica and P. uenonis are capable of substrate that is highly susceptible to proteolytic degradation
To understand if proteolytic activity might contribute to pathogenesis in the female genital tract, we Collagenase activity of P. asaccharolytica and P. uenonis was evaluated whether a common commensal vaginal microbe is evaluated using fluorescently quenched substrates
Summary
The vaginal microbiome of healthy reproductive-age women is typically characterized by low species diversity, with Lactobacillus dominating the vaginal and ectocervical niches of the lower genital tract[1,2]. P. asaccharolytica and P. uenonis colonize the vagina in 15–50% of healthy women and their prevalence and abundance increase with BV, they are typically considered low abundance taxa[13,16,17,18,19,20]. Recent studies show these species are predictors of spontaneous preterm labor[9,21], pelvic inflammatory disease[22,23], human papillomavirus (HPV) infections progressing to cervical neoplasia[24,25], and uterine cancer[26,27]. An improved understanding of the functional capacity of vaginal Porphyromonas species is needed
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