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.

Violent political extremists often point to online communities as motivating their behavior. However, researchers studying online exposure to extremism through structural mechanisms such as algorithms have not found strong evidence of their influence. At the same time, models of offline radicalization processes emphasize the importance of personal motivations, such as desire for significance and community, but do not fully account for online contexts. The authors integrate these approaches, which are both interested in worsening political extremism, asking, (1) What are the pathways to extreme content and communities online? and (2) What are the perceptions of extremism in online communities? Through interviews with politically active Redditors, the authors identify three motivations for initial engagement with fringe political communities: political unsorting of the self, political exceptionalism, and virtuous participation. The authors argue these motivations are potentially important seeds of political extremism and discuss the implications for supporting healthy political discourse online.

Recent research shows that “algorithmic radicalization” and “echo chambers”—the idea that recommendation algorithms on social media have a strong independent effect on radicalization and silo people into ideologically homogeneous communities—are not as prevalent nor influential as once feared. Yet, online political discourse is as toxic as ever while political misinformation continues to plague social media platforms. This begs the question: If algorithms aren’t encouraging radicalization, then what is producing it? Drawing from church-sect theory, this study interviews politically active Reddit users to better understand _how_ they arrived at their current media use, online engagement, and political beliefs. Results show that participants have a deep mistrust of mainstream media, leading them to seek alternative sources of political content. Reddit participation is also driven by a desire for “earnest” political discussions with like-minded individuals and cross-partisans, in part to “reject” partisan polarization. Despite engaging on more extreme subreddits, participants said their beliefs were unchanged, but that other Redditors had moved to more extreme beliefs over time. And, participants perceived their Reddit participation as necessary to _prevent_ radicalization and partisan polarization. Collectively, these results provide preliminary insight into the media and social/psychological pathways that could lead to online radicalization, providing an alternative explanation to algorithmic radicalization. This study also underscores the importance of interrogating the ecological pathways to radicalization for researchers and policy-makers; future interventions should account for attribution bias and the individual-level factors related to radicalization.

Porphyromonas asaccahrolytica and Porphyromonas uenonis are frequently isolated from the human vagina and are linked to bacterial vaginosis and preterm labour. 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. Given their phylogenetic relatedness, we hypothesized that vaginal Porphyromonas species possess gingipain-like protease activity targeting host extracellular matrix in the female reproductive tract. In this study, we demonstrate that vaginal Porphyromonas species degrade type I collagen (cervix), type IV collagen (chorioamnion/placenta), and fibrinogen, but not through the activity of gingipain orthologs. Bioinformatic queries identified five candidate collagenases in each species, including serine, cysteine and metalloproteases, with signal peptides directing them to the extracellular environment. Inhibition assays revealed both species secrete metalloproteases that degrade collagen and casein, while P. asaccharolytica also secretes a metalloprotease that degrades fibrinogen. Phylogenetic analysis of the predicted collagen-degrading metalloprotease revealed an orthologous relationship with the P. gingivalis endopeptidase PepO. Cloning and expression of P. asaccharolytica PepO confirmed this protein's collagenase and caseinase activities, which have not previously been attributed to PepO homologs in other bacteria. Altogether, this description of the first known virulence factor in Porphyromonas species colonizing the human vagina sheds light on their potential to alter the structural integrity and homeostasis of reproductive tissues.

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