Characterization of the Trichomonas vaginalis surface-associated AP65 and binding domain interacting with trichomonads and host cells

Garcia, Ana F.; Alderete, John F.

doi:10.1186/1471-2180-7-116

Cited by 40 publications

(55 citation statements)

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“…Although in the literature it is routinely reported that men infected by their partners resolve their infections, there is neither experimental evidence nor clinical studies proving this. Reports have shown the expression of numerous virulence factors that permit this ancient protist to survive in the changing host environment of the female urogenital region (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Iron is an important modulator of upregulation and downregulation of the expression of virulence genes (8,(19)(20)(21)(22)(23)(24)(25).…”

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confidence: 99%

Epitopes of the Highly Immunogenic Trichomonas vaginalis α-Actinin Are Serodiagnostic Targets for Both Women and Men

2013

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There is a need for a point-of-care serodiagnostic test for women and men for sexually transmitted infections (STIs) caused by Trichomonas vaginalis. Sera from women with this STI and sera from men that were analyzed in studies showing a relationship between serostatus and prostate cancer are highly seropositive in response to trichomonad ␣-actinin and its truncated protein (ACT-P2) (positive control sera). Epitope mapping experiments showed that positive control sera from women had antibodies to 13 distinct epitopes, 5 of which were detected by positive control sera from men. Sera from women and men that were unreactive with ␣-actinin (negative control sera) failed to detect any of the epitopes or other ␣-actinin amino acid sequences. The T. vaginalis ␣-actinin amino acid sequence and the sequences of the epitopes showed little or no identity with those of other proteins of microbial pathogens or the human ␣-actinin 1 (HuACTN1) homolog. Immunoassays such as dot blot, immunoblot, and enzyme-linked immunosorbent assays were used. Positive control sera did not detect HuACTN1 in immunoassays, and the range of levels of identity of ␣-actinin epitopes with HuACTN1 was 0% to 50%. Comparison of the T. vaginalis ␣-actinin epitopes with proteins in data banks, such as Tritrichomonas suis, Candida albicans, and Saccharomyces cerevisiae proteins, gave a range of identity levels of 0% to 22%. Specific 15-mer peptide epitopes of ␣-actinin with low to no identity with other proteins were synthesized and were reactive with positive control sera only. These findings identify epitopes of ␣-actinin as candidate serodiagnostic targets and suggest strongly that a highly seropositive reaction to ␣-actinin suggests exposure to T. vaginalis.T richomonas vaginalis is the most common nonviral causative agent for sexually transmitted infections (STIs). The adverse consequences for the health of women have been well documented (1, 2). Although in the literature it is routinely reported that men infected by their partners resolve their infections, there is neither experimental evidence nor clinical studies proving this. Reports have shown the expression of numerous virulence factors that permit this ancient protist to survive in the changing host environment of the female urogenital region (3-18). Iron is an important modulator of upregulation and downregulation of the expression of virulence genes (8,(19)(20)(21)(22)(23)(24)(25). Key steps for host colonization result from overcoming the urogenital mucous layer (18) in preparation for specific cytoadherence to vaginal epithelial cells (7,9,11,22,24). The intimacy of the host-parasite relationship during colonization and infection is exceedingly complex, as evidenced by the large number of proteinases (4,11,15,26) and the secretion by trichomonads of large amounts of putrescine for spermine uptake and back-conversion to spermidine (13,26). This coating of T. vaginalis by polyamines and host macromolecules affects levels of cytoadherence and cytotoxicity (3, 13).More recently, epidemiologic...

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Epitopes of the Highly Immunogenic Trichomonas vaginalis α-Actinin Are Serodiagnostic Targets for Both Women and Men

2013

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“…Several hydrogenosomal enzymes have previously been shown to be expressed on cell surfaces and mediate the cytoadherence of T. vaginalis when its growth medium was supplied with an excessive amount of iron (7,8,10). Although the secondary roles of these hydrogenosomal enzymes remain arguable, biochemical and genetic evidence suggests that a 65-kDa malic enzyme, referred to as AP65 and encoded by the ap65-1 gene, is likely involved in parasitic cytoadherence to human vaginal epithelial cells (11)(12)(13).…”

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Regulation of Nuclear Translocation of the Myb1 Transcription Factor by TvCyclophilin 1 in the Protozoan Parasite Trichomonas vaginalis

Hsu

Chu

Wang

et al. 2014

Journal of Biological Chemistry

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“…Preimmune (PI) serum was used as a negative control, and other primary antibodies were used to detect TvTIM and the control proteins in Western blotting (WB), including the following: anti-TvTIMr, an antibody previously generated against the recombinant TvTIM2 protein that recognizes both recombinant TvTIM proteins (23); anti-AP65, an antibody generated against the native AP65 trichomonad adhesin; anti-EhHKr, an antibody generated against the Entamoeba histolytica recombinant hexokinase that cross-reacts with T. vaginalis hexokinase (TvHK); and anti-TvENOr, an antibody generated against the recombinant T. vaginalis alpha-enolase (TvENO; TVAG_329460). The control proteins included the loading control; the adhesin AP65; TvHK, which is upregulated by glucose; and TvENO, which is not affected by glucose (12,29,30). These experiments were performed at least three independent times, with similar results.…”

Section: Methodsmentioning

confidence: 60%

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

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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...

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Characterization of the Trichomonas vaginalis surface-associated AP65 and binding domain interacting with trichomonads and host cells

Abstract: Background: AP65 is a prominent adhesin of Trichomonas vaginalis that mediates binding of parasites to host vaginal epithelial cells (VECs). AP65 with no secretion signal sequence, membrane targeting peptide, and anchoring motif was recently found to be secreted.

Cited by 40 publications

References 39 publications

Epitopes of the Highly Immunogenic Trichomonas vaginalis α-Actinin Are Serodiagnostic Targets for Both Women and Men

Epitopes of the Highly Immunogenic Trichomonas vaginalis α-Actinin Are Serodiagnostic Targets for Both Women and Men

Regulation of Nuclear Translocation of the Myb1 Transcription Factor by TvCyclophilin 1 in the Protozoan Parasite Trichomonas vaginalis

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

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