Deep sequencing of Trichomonas vaginalis during the early infection of vaginal epithelial cells and amoeboid transition

Gould, Sven B.; Woehle, Christian; Kusdian, Gary; Landan, Giddy; Tachezy, Jan; Zimorski, Verena; Martin, William

doi:10.1016/j.ijpara.2013.04.002

Cited by 78 publications

(104 citation statements)

References 66 publications

Supporting

Mentioning

102

Contrasting

Order By: Relevance

“…1B). These results are consistent with transcriptomic studies revealing the overexpression of tvtim2, but not tvtim1, in parasites grown under HG conditions (26) and in contact with vaginal epithelial cells (42) or with Fn (25). These data suggest that the transcription of the tvtim genes is differentially regulated during in vitro infection, in contact with ECM proteins such as Fn, and by glucose via stillunknown regulatory elements that control the expression of each gene, resulting in different functions and localizations.…”

Section: Discussionsupporting

confidence: 89%

“…For example, some glycolytic enzymes that are localized on the surface of T. vaginalis exhibit new functions as adhesins (6,8,9,29) or receptor molecules for ECM components, participating in hostparasite interactions (11,12). However, this topic has been controversial for the trichomonad community (4,(40)(41)(42), because like other moonlighting proteins (14,39), these molecules lack TMDs and SPs; the pathway used by the proteins to reach the parasite membrane is still unknown (14,39), and their receptors have not been identified yet. In this study, we demonstrated that glucose differentially regulates the expression of the two TvTIMencoding genes (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein

et al. 2016

View full text Add to dashboard Cite

dTriosephosphate isomerase of Trichomonas vaginalis (TvTIM) is a 27-kDa cytoplasmic protein encoded by two genes, tvtim1 and tvtim2, that participates in glucose metabolism. TvTIM is also localized to the parasite surface. Thus, the goal of this study was to identify the novel functions of the surface-associated TvTIM in T. vaginalis and to assess the effect of glucose as an environmental factor that regulates its expression and localization. Reverse transcription-PCR (RT-PCR) showed that the tvtim genes were differentially expressed in response to glucose concentration. tvtim1 was overexpressed under glucose-restricted (GR) conditions, whereas tvtim2 was overexpressed under glucose-rich, or high-glucose (HG), conditions. Western blot and indirect immunofluorescence assays also showed that glucose positively affected the amount and surface localization of TvTIM in T. vaginalis. Affinity ligand assays demonstrated that the recombinant TvTIM1 and TvTIM2 proteins bound to laminin (Lm) and fibronectin (Fn) but not to plasminogen. Moreover, higher levels of adherence to Lm and Fn were detected in parasites grown under HG conditions than in those grown under GR conditions. Furthermore, pretreatment of trichomonads with an anti-TvTIMr polyclonal antibody or pretreatment of Lm-or Fn-coated wells with both recombinant proteins (TvTIM1r and TvTIM2r) specifically reduced the binding of live parasites to Lm and Fn in a concentration-dependent manner. Moreover, T. vaginalis was exposed to different glucose concentrations during vaginal infection of women with trichomoniasis. Our data indicate that TvTIM is a surface-associated protein under HG conditions that mediates specific binding to Lm and Fn as a novel virulence factor of T. vaginalis.T richomonas vaginalis is a protozoan parasite responsible for human trichomoniasis, the most common nonviral sexually transmitted infection, which affects over 276 million people annually worldwide (1). Infection with this organism is associated with severe health complications, such as vaginitis, preterm delivery, urethritis, prostatitis, infertility, and increases in the risks of prostate and cervical cancer. It has also been implicated in facilitating the infection and transmission of human immunodeficiency virus (HIV) (2-4).To establish an infection in the vagina, T. vaginalis must cross the vaginal mucus, adhere to the vaginal and cervical epithelia, and multiply in and colonize the urogenital tract (2, 5). The vagina is one of the most complex mucosal microenvironments and is constantly changing during the menstrual cycle. However, in vitro studies have shown that T. vaginalis adapts and responds to these changes, modulating the expression of multiple genes, including those encoding virulence factors, to maintain a chronic infection (6).Energy generation is vital to the maintenance of chronic infection and depends on the availability of nutrients, such as iron and a carbon source. For T. vaginalis, glucose is the major energy source under both anaerobic and aerobic conditions. With...

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein

et al. 2016

View full text Add to dashboard Cite

show abstract

“…When in contact with epithelial cells, the typically ovoid T. vaginalis cell morphologically adjusts, assuming an amoeboid conformation (Gould et al, 2013). The cells attach to the epithelial surface, with the amoeboid morphology enabling the parasite to increase the surface area contact, and interaction, with the epithelial cell.…”

Section: Pathogenesismentioning

confidence: 99%

Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis

Edwards

Burke

Smalley

et al. 2014

Critical Reviews in Microbiology

View full text Add to dashboard Cite

Trichomonas vaginalis is the etiological agent of trichomoniasis, the most prevalent non-viral sexually transmitted disease worldwide. Trichomoniasis is a widespread, global health concern, and occurring at an increasing rate. Infections of the female genital tract can cause a range of symptoms, including vaginitis and cervicitis, whilst infections in males are generally asymptomatic. The relatively mild symptoms, and lack of evidence for any serious sequelae, have historically led to this disease being under diagnosed, and under researched. However, growing evidence that T. vaginalis infection is associated with disease states with high morbidity in both men and women has increased the efforts to diagnose and treat patients harbouring this parasite. The pathology of trichomoniasis results from damage to the host epithelia, caused by a variety of processes during infection, and recent work has highlighted the complex interactions between the parasite and host, commensal microbiome, and accompanying symbionts. The commercial release of a number of nucleic acid amplification tests (NAATs) has added to the available diagnostic options. Immunoassay based Point of Care testing is currently available, and a recent initial evaluation of a NAAT Point of Care system has given promising results, which would enable testing and treatment in a single visit.

show abstract

“…The heavily duplicated trichomonas genome accepts and rejects horizontally transferred genes of prokaryotic derivation [40], carries dsRNA and totiviridae genomes [41][42][43], harbors inserted retrotransposons (Tc1/ mariner, Kolobok) [44,45], and practices morphological transformation of a fl agellate entity into an amoeboid parasite [46,47].…”

Section: Trichomonasmentioning

confidence: 99%

The cell survival pathways of the primordial RNA-DNA complex remain conserved in the extant genomes and may function as proto-oncogenes

Sinkovics¹

2015

European Journal of Microbiology and Immunology

View full text Add to dashboard Cite

Malignantly transformed (cancer) cells of multicellular hosts, including human cells, operate activated biochemical pathways that recognizably derived from unicellular ancestors. The descendant heat shock proteins of thermophile archaea now chaperon oncoproteins. The ABC cassettes of toxin-producer zooxantella Symbiodinia algae pump out the cytoplasmic toxin molecules; malignantly transformed cells utilize the derivatives of these cassettes to get rid of chemotherapeuticals. High mobility group helixloop-helix proteins, protein arginine methyltransferases, proliferating cell nuclear antigens, and Ki-67 nuclear proteins, that protect and repair DNA in unicellular life forms, support oncogenes in transformed cells. The cell survival pathways of Wnt-β-catenin, Hedgehog, PI3K, MAPK-ERK, STAT, Ets, JAK, Pak, Myb, achaete scute, circadian rhythms, Bruton kinase and others, which are physiological in uni-and early multicellular eukaryotic life forms, are constitutively encoded in complex oncogenic pathways in selected single cells of advanced multicellular eukaryotic hosts. Oncogenes and oncoproteins in advanced multicellular hosts recreate selected independently living and immortalized unicellular life forms, which are similar to extinct and extant protists. These uni cellular life forms are recognized at the clinics as autologous "cancer cells".

show abstract

Deep sequencing of Trichomonas vaginalis during the early infection of vaginal epithelial cells and amoeboid transition

Cited by 78 publications

References 66 publications

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein

The Glycolytic Enzyme Triosephosphate Isomerase of Trichomonas vaginalis Is a Surface-Associated Protein Induced by Glucose That Functions as a Laminin- and Fibronectin-Binding Protein

Trichomonas vaginalis: Clinical relevance, pathogenicity and diagnosis

The cell survival pathways of the primordial RNA-DNA complex remain conserved in the extant genomes and may function as proto-oncogenes

Contact Info

Product

Resources

About