We describe the genome sequence of the protist Trichomonas vaginalis , a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the ∼160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.

Significance: Prostate cancer is the most common nonskin cancer in America and the fifth most common cancer worldwide. Inflammation is implicated in the initiation and progression of prostate cancer; however, sources of inflammation remain unidentified. Trichomonas vaginalis is a prevalent parasite that infects prostate epithelium and is associated with an increase in aggressive prostate cancer. Here, we demonstrate that a secreted T. vaginalis protein homologous to human macrophage migration inhibitory factor elicits antibodies in infected individuals, increases prostate cell proliferation and invasiveness, and induces cellular pathways linked to inflammation. This study demonstrates that a specific parasite-derived protein can mimic its human homolog to increase inflammation and cell proliferation, which, in turn, may result in the promotion and progression of prostate cancer.

Objectives: Trichomonas vaginalisis the causative agent of trichomoniasis, one of the most common sexually transmitted diseases worldwide. In recent years we have described the symbiotic relationship betweenT vaginalisandMycoplasma hominis. How this biological association might affect the pathogenicity of one or both the microorganisms is still unknown. Since local inflammation is thought to play a central role inT vaginalisinfection, we investigated the in vitro response of human macrophages to naturally mycoplasma-freeT vaginalis, as compared to a mycoplasma-infected trichomonad isolate.Methods: THP-1 cells were stimulated with two isogenicT vaginalisisolates, one naturally mycoplasma-free and one stably associated withM hominis, and secreted cytokines measured by ELISA. Nuclear factor κB (NFκB) involvement in THP-1 response toT vaginalisandM hominiswas evaluated by means of a reporter system based on detection of alkaline phosphatase activity.Results: We found that the presence ofM hominisupregulates the expression of a panel of proinflammatory cytokines in a synergistic fashion. We also found that the upregulation of the proinflammatory response by THP-1 cells involves the transcription factor NFκB.Conclusions: These findings suggest that the presence ofM hominisinT vaginalisisolates might play a key role in inflammation during trichomoniasis, thus affecting the severity of the disease. The synergistic upregulation of the macrophage proinflammatory response might also affect some important clinical conditions associated withT vaginalisinfection, such as the increased risk of acquiring cervical cancer or HIV, which are thought to be affected by the inflammatory milieu during trichomoniasis.

The existence of a symbiotic relationship between Trichomonas vaginalis and Mycoplasma hominis , which is the first reported example of symbiosis between two obligate human pathogens, has been recently reported by our research group. In this work, we examined the cellular location of M. hominis in respect to T. vaginalis . By using gentamicin protection assays, double immunofluorescence, and confocal microscopy, we obtained strong evidence that M. hominis is located within protozoan cells. 5-Bromodeoxyuridine incorporation assays showed that intracellularly located mycoplasmas actively synthesize DNA. Our results demonstrate that M. hominis has the capability of entering trichomonad cells and of replicating inside the protozoon. These findings suggest that symbiosis might provide the bacteria, during human infection, with the capability to resist to environmental stresses, such as host defense mechanisms and pharmacological therapies.