Abstract
Pore-forming proteins (PFPs) are a group of functionally versatile molecules distributed in all domains of life, and several microbial pathogens notably use members of this class of proteins as cytotoxic effectors. Among pathogenic protists, Entamoeba histolytica, and Naegleria fowleri display a range of pore-forming toxins belonging to the Saposin-Like Proteins (Saplip) family: Amoebapores and Naegleriapores. Following the genome sequencing of Trichomonas vaginalis, we identified a gene family of 12 predicted saposin-like proteins (TvSaplips): this work focuses on investigating the potential role of TvSaplips as cytopathogenetic effectors. We provide evidence that TvSaplip12 gene expression is potently upregulated upon T. vaginalis contact with target cells. We cloned and expressed recombinant TvSaplip12 in planta and we demonstrate haemolytic, cytotoxic, and bactericidal activities of rTvSaplip12 in vitro. Also, evidence for TvSaplip subcellular discrete distribution in cytoplasmic granules is presented. Altogether, our results highlight the importance of TvSaplip in T. vaginalis pathogenesis, depicting its involvement in the cytolytic and bactericidal activities during the infection process, leading to predation on host cells and resident vaginal microbiota for essential nutrients acquisition. This hence suggests a potential key role for TvSaplip12 in T. vaginalis pathogenesis as a candidate Trichopore.
Highlights
Trichomonas vaginalis is a pathogenic protist responsible for human trichomoniasis, the most common non-viral sexually transmitted infection, with more than 156 million cases reported every year worldwide (Rowley et al, 2019)
The current view of trichomoniasis pathogenesis leading to host tissue damage involves on the one side the host inflammatory response, and on the other side the cytopathic effect exerted by the direct action of toxic proteins expressed by T. vaginalis (Mercer and Johnson, 2018)
In order to identify gene products potentially involved in T. vaginalis-induced haemolysis, the expression of TvSaplip genes upon contact with human red blood cells (RBCs) was evaluated in quantitative Reverse Transcription PCR (qRT-PCR) in a time-course experiment
Summary
Trichomonas vaginalis is a pathogenic protist responsible for human trichomoniasis, the most common non-viral sexually transmitted infection, with more than 156 million cases reported every year worldwide (Rowley et al, 2019). Multiple mechanisms are involved in the colonization of the vaginal mucosa by T. vaginalis, with parasite adherence to target cells being a relevant step in pathogenicity (Fiori et al, 1997; Hirt et al, 2007; Lustig et al, 2013). The current view of trichomoniasis pathogenesis leading to host tissue damage involves on the one side the host inflammatory response, and on the other side the cytopathic effect exerted by the direct action of toxic proteins expressed by T. vaginalis (Mercer and Johnson, 2018). A number of proteins, mainly proteases, have been involved in the direct cytopathic effect mediated by T. vaginalis over epithelial target cells. In the past years we focused our efforts on the characterization of T. vaginalis-mediated heamolysis in vitro, showing a pore-forming activity leading to osmotic lysis of target cells in a pH, temperature, and Ca2+-dependent fashion (Fiori et al, 1993, 1996, 1997). Despite the detailed description of functional pore formation onto the membranes of target cells by T. vaginalis, the proteins putatively involved in this phenomenon have not been identified yet
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