Enzymes on microbial pathogens and<i>Trichomonas vaginalis</i>: molecular mimicry and functional diversity

Alderete, John F.; Millsap, Kevin W.; Lehker, Michael W.; Benchimol, Marlene

doi:10.1046/j.1462-5822.2001.00126.x

Cited by 51 publications

(56 citation statements)

References 97 publications

(131 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The presence of multigene families for expression of proteins is often observed in T. vaginalis genome [43]. As a mucosal pathogen, T. vaginalis should efficiently adapt to different environments such as alterations in extracellular nucleotide concentrations, hence more than one NTPDase gene sequence could collaborate to this aim.…”

Section: Discussionmentioning

confidence: 99%

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Frasson

Carli

Bonan

et al. 2011

Purinergic Signalling

View full text Add to dashboard Cite

Trichomonas vaginalis is a parasite from the human urogenital tract that causes trichomonosis, the most prevalent non-viral sexually transmitted disease. The neutrophil infiltration has been considered to be primarily responsible for cytological changes observed at infection site, and the chemoattractants can play an important role in this leukocytic recruitment. Nitric oxide (NO) is one of the most widespread mediator compounds, and it is implicated in modulation of immunological mechanisms. Extracellular nucleotides and nucleosides are signaling molecules involved in several processes, including immune responses and control of leukocyte trafficking. Ectonucleoside triphosphate diphosphohydrolase members, ecto-5′-nucleotidase, and adenosine deaminase (ectoADA) have been characterized in T. vaginalis. Herein, we investigated the effects of purinergic system on NO production by neutrophils stimulated with T. vaginalis. The trophozoites were able to induce a high NO synthesis by neutrophils through iNOS pathway. The extracellular nucleotides ATP, ADP, and ATPγS (a nonhydrolyzable ATP analog) showed no significant change in NO secretion. In contrast, adenosine and its degradation product, inosine, promoted a low production of the compound. The immunosuppressive effect of adenosine upon NO release by neutrophils occurred due to adenosine A 2A receptor activation. The ecto-5′-nucleotidase activity displayed by T. vaginalis was shown to be important in adenosine generation, indicating the efficiency of purinergic cascade. Our data suggest the influence of purinergic signaling, specifically adenosinergic system, on NO production by neutrophils in T. vaginalis infection, contributing to the immunological aspects of disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Frasson

Carli

Bonan

et al. 2011

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…Briefly and as before (6,24), trichomonads were fixed overnight at room temperature in 2.5% (vol/vol) glutaraldehyde (Sigma) in 0.1 M cacodylate (Sigma) buffer (pH 7.2). The cells were then washed twice in phosphate-buffered saline (PBS).…”

Section: Methodsmentioning

confidence: 99%

Trichomonas vaginalis Polyamine Metabolism Is Linked to Host Cell Adherence and Cytotoxicity

2005

View full text Add to dashboard Cite

Trichomonas vaginalis secretes putrescine that is readily detected in vaginal secretions. We wanted to examine the effect of decreased putrescine synthesis by inhibition of ornithine decarboxylase (ODC) on T. vaginalis. One reason is because inhibition of Tritrichomonas foetus ODC results in growth arrest, destruction of hydrogenosomes, and decreased amounts of hydrogenosomal enzymes. Treatment of T. vaginalis T016 with >20 mM 1,4-diamino-2-butanone (DAB) to inhibit ODC resulted in growth arrest, which was reversed by addition of exogenous putrescine. No similar reversal of growth arrest was achieved with the polyamines spermine or spermidine or with iron. Electron microscopic examination of control versus DAB-treated trichomonads did not reveal any adverse effects on the number and integrity of hydrogenosomes. Further, the adhesins AP65, AP51, and AP33 mediating binding to immortalized vaginal epithelial cells (VECs) share identity to enzymes of the hydrogenosome organelle, and there was no difference in amounts of adhesins between control versus DAB-treated T. vaginalis parasites. Likewise, similar patterns and extent of fluorescence were evident for the prominent AP65 adhesin. Surprisingly, DAB treatment increased by 4-to 20-fold above untreated trichomonads handled identically the level of adherence mediated by adhesins. Interestingly, the enhanced attachment to VECs was reversed by exogenous putrescine added to DAB-treated trichomonads. Equally noteworthy was that DAB-treated T. vaginalis with enhanced adherence did not possess the previously reported ability to kill host cells in a contact-dependent fashion mediated by cysteine proteinases, and total cysteine proteinase activity patterns were identical between control and DAB-treated trichomonads. Overall, these data suggest that polyamine metabolism and secreted putrescine are linked to host cell adherence and cytotoxicity.

show abstract

“…Cytoadherence, which is crucial for T. vaginalis to establish an infection, has been shown to involve multiple surface adhesion proteins and lipophosphoglycans (2)(3)(4). The iron supply, which undergoes periodic fluctuations in the human vagina, is one of the principle determinants modulating cytoadherence of the parasite toward human vaginal epithelial cells (5,6), possibly through transcriptional regulation of some of the adhesion protein (ap) 2 genes, especially those in the ap65 family (7,8), which encode proteins identical to malic enzymes (9,10). Iron has also been implicated in modulating phenotypic variation of the parasite as well as its resistance to complement lysis (11,12).…”

mentioning

confidence: 99%

Activation of Multifarious Transcription of an Adhesion Protein ap65-1 Gene by a Novel Myb2 Protein in the Protozoan Parasite Trichomonas vaginalis

Ong

Hsu

Liu

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Multifarious transcription of the adhesion protein ap65-1 gene in the human pathogen, Trichomonas vaginalis, is critically regulated by the coordination of two similar but opposite oriented DNA regulatory regions, MRE-1/MRE-2r and MRE-2f, both of which are binding sites for multiple Myb-like proteins. In the present study, MRE-1/MRE-2r was demonstrated to be composed of multiple overlapping promoter elements, among which the entire region is required for growth-related ap65-1 transcription, and the 5-MRE-1 antagonizes the suppressive activity of the 3-MRE-2r in iron-inducible transcription. The recombinant Myb2 protein derived from a previously identified myb2 gene was demonstrated to recognize distinct sequence contexts in MRE-2r and MRE-2f, whereas Myb2 in the nuclear lysate preferentially binds to MRE-2f to MRE-2r. Iron repletion resulted in persistent repression of the myb2 gene, and temporal activation/deactivation of Myb2 promoter entry, which was also activated by prolonged iron depletion. The hemagglutinintagged Myb2 when overexpressed during iron-depleted conditions facilitated basal and growth-related ap65-1 transcription to a level that was achieved in iron-replete cells, whereas ironinducible ap65-1 transcription was abolished with knockdown of Myb2. These findings demonstrated that Myb2 is involved in activation of growth-related and iron-inducible transcription of the ap65-1 gene, possibly through differential promoter selection in competition with other Myb proteins.Trichomonas vaginalis is a protozoan parasite that causes the most common sexually transmitted disease of nonviral origin in humans. The disease poses an imminent threat to public health as revealed by recent findings that transmission of the human immunodeficiency virus increases in patients with trichomoniasis (1). The parasite persistently inhabits the human urogenital tract without an alternating life stage outside of the host. Cytoadherence, which is crucial for T. vaginalis to establish an infection, has been shown to involve multiple surface adhesion proteins and lipophosphoglycans (2-4). The iron supply, which undergoes periodic fluctuations in the human vagina, is one of the principle determinants modulating cytoadherence of the parasite toward human vaginal epithelial cells (5, 6), possibly through transcriptional regulation of some of the adhesion protein (ap) 2 genes, especially those in the ap65 family (7, 8), which encode proteins identical to malic enzymes (9, 10). Iron has also been implicated in modulating phenotypic variation of the parasite as well as its resistance to complement lysis (11, 12). These observations underscore the importance of iron in modulating expression of parasite virulence.Gene transcription in T. vaginalis is monocistronic with only a few intron-containing genes capable of undergoing RNA splicing (13). Transcription initiation by RNA polymerase II is thus a key step in controlling expression of the protein coding genes in the parasite. Using transcription of the ap65-1 gene as a model system, we...

show abstract

Enzymes on microbial pathogens andTrichomonas vaginalis: molecular mimicry and functional diversity

Cited by 51 publications

References 97 publications

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Involvement of purinergic signaling on nitric oxide production by neutrophils stimulated with Trichomonas vaginalis

Trichomonas vaginalis Polyamine Metabolism Is Linked to Host Cell Adherence and Cytotoxicity

Activation of Multifarious Transcription of an Adhesion Protein ap65-1 Gene by a Novel Myb2 Protein in the Protozoan Parasite Trichomonas vaginalis

Contact Info

Product

Resources

About