Trichomonas vaginalis vast BspA-like gene family: evidence for functional diversity from structural organisation and transcriptomics

Abstract

BackgroundTrichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of T. vaginalis genome identified a plethora of candidate extracellular proteins.ResultsData mining of the T. vaginalis genome identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich repeats, which represent the largest gene family encoding potential extracellular proteins for the pathogen. A broad range of microorganisms encoding BspA-like proteins was identified and these are mainly known to live on mucosal surfaces, among these T. vaginalis is endowed with the largest gene family. Over 190 TvBspA proteins with inferred transmembrane domains were characterised by a considerable structural diversity between their TpLRR and other types of repetitive sequences and two subfamilies possessed distinct classic sorting signal motifs for endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with proteins from Clostridium difficile pathogenic strains and C. difficile phages. Consistent with the hypothesis that TvBspA protein structural diversity implies diverse roles, we demonstrated for several TvBspA genes differential expression at the transcript level in different growth conditions. Identified variants of repetitive segments between several TvBspA paralogues and orthologues from two clinical isolates were also consistent with TpLRR and other repetitive sequences to be functionally important. For one TvBspA protein cell surface expression and antibody responses by both female and male T. vaginalis infected patients were also demonstrated.ConclusionsThe biased mucosal habitat for microbial species encoding BspA-like proteins, the characterisation of a vast structural diversity for the TvBspA proteins, differential expression of a subset of TvBspA genes and the cellular localisation and immunological data for one TvBspA; all point to the importance of the TvBspA proteins to various aspects of T. vaginalis pathobiology at the host-pathogen interface.

The biology of Trichomonas vaginalis in the light of urogenital tract infection

“…The largest surface protein family identified in Trichomonas are the BspA (Bacteroides surface protein A)-like proteins [49]. The parasite encodes 911 BspA-like proteins, expression evidence exists for 721 of them [14] and they have been shown to localise to the parasite's surface [49].…”

“…vaginalis does not encode a machinery that would allow the parasite to equip proteins with glycosylphosphatidylinositol (GPI)-anchors that are ubiquitous in other eukaryotes [10,47] and, with respect to protist parasites, often stimulate the host immune response [48]. Still, the surface of T. vaginalis is covered by a highly variable coat of proteins whose number might reach into the hundreds [39,44,49], and while some proteins are found exposed more frequently on the surface of more virulent strains than others [50], again their function remains unknown. Next to the many glycoproteins, different adhesion proteins and receptors cover the surface that provide the basis for ligand-receptor binding [51].…”

The effects of environmental factors on the virulence of Trichomonas vaginalis

“…TvBspA could also mediate endocytosis of different host proteins and viruses, as well as underpin phagocytosis of bacteria and various host cells. Finally, TvBspA proteins could orchestrate the modulation of the innate immune system through TLRs signaling during infection and mediate immune evasion through differential expression [34]. The T. vaginalis dense glycocalyx corresponds to the outer layer on its cell membrane formed by different carbohydrateassociated molecules, such as lipophosphoglycan (LPG)-like, glycoproteins, and glycolipids.…”

Dientamoeba fragilis, the Neglected Trichomonad of the Human Bowel

“…Trophozoites of D. fragilis were also described as being metabolically similar to those of T. vaginalis (41). Like T. vaginalis, D. fragilis has also undergone a massive expansion in its repertoire of BspA-like leucine-rich repeats (44) and actin family genes (43), among several others (41).…”