Lactobacillus gasseri and Gardnerella vaginalis produce extracellular vesicles that contribute to the function of the vaginal microbiome and modulate host- Trichomonas vaginalis interactions

Trichomonas vaginalis is an extracellular protozoan parasite of the human urogenital tract, responsible for a prevalent sexually transmitted infection. Trichomoniasis is accompanied by a dysbiotic microbiome that is characterised by the depletion of host-protective commensals such as Lactobacillus gasseri, and the flourishing of a bacterial consortium that is comparable to the one seen for bacterial vaginosis, including the founder species Gardnerella vaginalis. These two vaginal bacteria are known to have opposite effects on T. vaginalis pathogenicity. Studies on extracellular vesicles (EVs) have been focused on the direction of a microbial producer (commensal or pathogen) to a host recipient, and largely in the context of the gut microbiome. Here, taking advantage of the simplicity of the human cervicovaginal microbiome, we determined the molecular cargo of EVs produced by L. gasseri and G. vaginalis and examined how these vesicles modulate the interaction of T. vaginalis and host cells. We show that these EVs carry a specific cargo of proteins, which functions can be attributed to the opposite roles that these bacteria play in the vaginal biome. Furthermore, these bacterial EVs are delivered to host and protozoan cells, modulating host-pathogen interactions in a way that mimics the opposite effects that these bacteria have on T. vaginalis pathogenicity. This is the first study to describe side-by-side the protein composition of EVs produced by two bacteria belonging to the opposite spectrum of a microbiome and to demonstrate that these vesicles modulate the pathogenicity of a protozoan parasite. Such as in trichomoniasis, infections and dysbiosis co-occur frequently resulting in significant co-morbidities. Therefore, studies like this provide the knowledge for the development of antimicrobial therapies that aim to clear the infection while restoring a healthy microbiome.