Polyamine depletion down-regulates expression of the Trichomonas vaginalis cytotoxic CP65, a 65-kDa cysteine proteinase involved in cellular damage

Álvarez-Sánchez, María Elizbeth; Carvajal-Gamez, Bertha Isabel; Solano-González, Eduardo; Martínez-Benitez, Máximo; Garcia, Ana F.; Alderete, John F.; Arroyo, Rossana

doi:10.1016/j.biocel.2008.04.023

Cited by 28 publications

(25 citation statements)

References 52 publications

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“…In T. vaginalis, the inhibition of polyamine synthesis increases T. vaginalis adherence to VECs [65], but reduces trichomonal cytotoxicity. This could be due to the requirement of polyamines for expression of TvCP65 and TvCP39, two surfacelocated CPs involved in cytotoxicity [3,42,45,46]. The expression of TvCP65 and TvCP39 requires polyamines, possible at the post-transcriptional level by a mechanism mediated by polyamines [3], perhaps through RNAeprotein interactions, in which the T. vaginalis eukaryotic translation initiation factor 5A (TveIF-5A) may be involved.…”

Section: The Effect Of Polyamines On the Expression Of Virulence Genesmentioning

confidence: 97%

“…Many CPs play important roles in the virulence of parasites and are involved in cytoadherence [27e30], cytotoxicity [42,45,46], disruption of the host cell membrane cytoskeleton [9], degradation of the secretory leukocyte protease inhibitor [61], hemolysis [49], and human immunoglobulins [53]. Interestingly, the expression, proteolytic activity, and surface localization of certain trichomonad CPs are differentially modulated by iron, zinc, and polyamines in the medium [3,6,60], among other environmental signals.…”

Section: The Effect Of Iron and Cellular Contact In The Expression Ofmentioning

confidence: 99%

“…vaginalis responds to drastic environmental changes (e.g., temperature, microflora, pH, iron, polyamines, zinc, host immune responses, and other unknown factors), modulating the expression of multiple genes, including those encoding virulence factors, to maintain a chronic infection [1,3,4]. Additionally, because this parasite is microaerophilic, it requires defense molecules to neutralize the effects of oxygen.…”

Section: Introductionmentioning

confidence: 99%

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The effects of environmental factors on the virulence of Trichomonas vaginalis

Figueroa-Angulo

Rendón-Gandarilla

Puente-Rivera

et al. 2012

Microbes and Infection

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115

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Section: The Effect Of Polyamines On the Expression Of Virulence Genesmentioning

confidence: 97%

Section: The Effect Of Iron and Cellular Contact In The Expression Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The effects of environmental factors on the virulence of Trichomonas vaginalis

Figueroa-Angulo

Rendón-Gandarilla

Puente-Rivera

et al. 2012

Microbes and Infection

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115

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“…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).…”

mentioning

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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“…This is not the first protease discovered that is up-regulated by the presence of certain cations from the host. For example, Fe 2ϩ and polyamines, present in the female microenvironment, down-regulate the protein expression levels and the transcript of TvCP65 (41). In contrast, the amount of mRNA and protein of TvMP50 were up-regulated in the presence of Zn 2ϩ .…”

Section: Discussionmentioning

confidence: 89%

TvMP50 is an Immunogenic Metalloproteinase during Male Trichomoniasis

Quintas-Granados

Villalpando

Vázquez-Carrillo

et al. 2013

Molecular & Cellular Proteomics

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Trichomonas vaginalis, a human urogenital tract parasite, is capable of surviving in the male microenvironment, despite of the presence of Zn 2؉ . Concentrations > 1.6 mM of Zn 2؉ have a trichomonacidal effect; however, in the presence of <1.6 mM Zn 2؉ , several trichomonad proteins are up-or down-regulated. Herein, we analyzed the proteome of a T. vaginalis male isolate (HGMN01) grown in the presence of Zn 2؉ and found 32 protein spots that were immunorecognized by male trichomoniasis patient serum. Using mass spectrometry (MS), the proteins were identified and compared with 23 spots that were immunorecognized in the proteome of a female isolate using the same serum. Interestingly, we found a 50-kDa metallopeptidase (TvMP50). Unexpectedly, this proteinase was immunodetected by the serum of male trichomoniasis patients but not by the female patient serum or sera from healthy men and women. We analyzed the T. vaginalis genome and localized the mp50 gene in locus TVAG_403460. Using an RT-PCR assay, we amplified a 1320-bp mp50 mRNA transcript that was expressed in the presence of Zn 2؉ in the HGMN01 and CNCD147 T. vaginalis isolates. According to a Western blot assay, native TvMP50 was differentially expressed in the presence of Zn 2؉ . The TvMP50 proteolytic activity increased in the presence of Zn 2؉ in both isolates and was inhibited by EDTA but not by ptosyl-L-lysine chloromethyl ketone (TLCK), E64, leupeptin, or phenylmethane sulfonyl fluoride. Furthermore, the recombinant TvMP50 had proteolytic activity that was inhibited by EDTA. These data suggested that TvMP50 is immunogenic during male trichomoniasis, and Zn 2؉ induces its expression. Molecular & Cellular

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Polyamine depletion down-regulates expression of the Trichomonas vaginalis cytotoxic CP65, a 65-kDa cysteine proteinase involved in cellular damage

Cited by 28 publications

References 52 publications

The effects of environmental factors on the virulence of Trichomonas vaginalis

The effects of environmental factors on the virulence of Trichomonas vaginalis

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

TvMP50 is an Immunogenic Metalloproteinase during Male Trichomoniasis

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