Adenosine is the primary precursor of all purine nucleotides in Trichomonas vaginalis

Munagala, Narsimha R.; Wang, Ching C.

doi:10.1016/s0166-6851(02)00330-4

Cited by 37 publications

(48 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The concentration of free purine nucleotides in the vagina during disease can reach 10 mM as they are released from epithelial cells lysed during infection, and 90% of the nucleotides released are ATP (106). ATP itself is cytolytic toward mammalian cells not expressing NTPDase activity on their surface (58), but ATP does not lyse T. vaginalis, which may be a result of hydrolysis of ATP by the parasite.…”

Section: Trichomonas Vaginalismentioning

confidence: 99%

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Sansom

Robson

Hartland

2008

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARYIn humans, purinergic signaling plays an important role in the modulation of immune responses through specific receptors that recognize nucleoside tri- and diphosphates as signaling molecules. Ecto-nucleoside triphosphate diphosphohydrolases (ecto-NTPDases) have important roles in the regulation of purinergic signaling by controlling levels of extracellular nucleotides. This process is key to pathophysiological protective responses such as hemostasis and inflammation. Ecto-NTPDases are found in all higher eukaryotes, and recently it has become apparent that a number of important parasitic pathogens of humans express surface-located NTPDases that have been linked to virulence. For those parasites that are purine auxotrophs, these enzymes may play an important role in purine scavenging, although they may also influence the host response to infection. Although ecto-NTPDases are rare in bacteria, expression of a secreted NTPDase in Legionella pneumophila was recently described. This ecto-enzyme enhances intracellular growth of the bacterium and potentially affects virulence. This discovery represents an important advance in the understanding of the contribution of other microbial NTPDases to host-pathogen interactions. Here we review other progress made to date in the characterization of ecto-NTPDases from microbial pathogens, how they differ from mammalian enzymes, and their association with organism viability and virulence. In addition, we postulate how ecto-NTPDases may contribute to the host-pathogen interaction by reviewing the effect of selected microbial pathogens on purinergic signaling. Finally, we raise the possibility of targeting ecto-NTPDases in the development of novel anti-infective agents based on potential structural and clear enzymatic differences from the mammalian ecto-NTPDases.

show abstract

Section: Trichomonas Vaginalismentioning

confidence: 99%

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Sansom

Robson

Hartland

2008

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

show abstract

“…vaginalis is also a protozoan parasite with a relatively simple scheme for purine salvage (15), albeit one that is quite distinct from those in T. fetus and G. lamblia. It relies on the functions of two pivotal enzymes, purine nucleoside phosphorylase (PNP), 1 which catalyzes interconversion between purine bases and the corresponding purine nucleosides, and purine nucleoside kinase (PNK), which converts nucleosides to the nucleotides (16 -18).…”

mentioning

confidence: 99%

Identification of a Subversive Substrate of Trichomonas vaginalis Purine Nucleoside Phosphorylase and the Crystal Structure of the Enzyme-Substrate Complex

Zang

Wang

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Trichomonas vaginalis is an anaerobic protozoan parasite that causes trichomoniasis, a common sexually transmitted disease with worldwide impact. One of the pivotal enzymes in its purine salvage pathway, purine nucleoside phosphorylase (PNP), shows physical properties and substrate specificities similar to those of the high molecular mass bacterial PNPs but differing from those of human PNP. While carrying out studies to identify inhibitors of T. vaginalis PNP (TvPNP), we discovered that the nontoxic nucleoside analogue 2-fluoro-2-deoxyadenosine (F-dAdo) is a "subversive substrate." Phosphorolysis by TvPNP of F-dAdo, which is not a substrate for human PNP, releases highly cytotoxic 2-fluoroadenine (F-Ade). In vitro studies showed that both F-dAdo and F-Ade exert strong inhibition of T. vaginalis growth with estimated IC 50 values of 106 and 84 nM, respectively, suggesting that F-dAdo might be useful as a potential chemotherapeutic agent against T. vaginalis. To understand the basis of TvPNP specificity, the structures of TvPNP complexed with F-dAdo, 2-fluoroadenosine, formycin A, adenosine, inosine, or 2-deoxyinosine were determined by x-ray crystallography with resolutions ranging from 2.4 to 2.9 Å. These studies showed that the quaternary structure, monomer fold, and active site are similar to those of Escherichia coli PNP. The principal active site difference is at Thr-156, which is alanine in E. coli PNP. In the complex of TvPNP with F-dAdo, Thr-156 causes the purine base to tilt and shift by 0.5 Å as compared with the binding scheme of F-dAdo in E. coli PNP. The structures of the TvPNP complexes suggest opportunities for further improved subversive substrates beyond F-dAdo.

show abstract

“…Our laboratory has characterized an ecto-5′-nucleotidase activity in trophozoites of T. vaginalis (Tasca et al 2003) and Trichomonas gallinae (Borges et al 2007), and ultrastructural cytochemical microscopy has shown ecto-5′-nucleotidase activity on the surface of the parasite (Tasca et al 2004). The presence of an enzyme that hydrolyzes AMP to adenosine provides the nucleoside required for parasite growth due to the lack of de novo purine nucleotide synthesis among all trichomonad species (Wang 1990;Munagala and Wang 2003).…”

Section: Introductionmentioning

confidence: 99%

Steroid hormones alter AMP hydrolysis in intact trophozoites of Trichomonas vaginalis

et al. 2009

View full text Add to dashboard Cite

Trichomonas vaginalis infection may be influenced by the vaginal concentrations of estrogens. We have investigated the effects of 17beta-estradiol and dehydroepiandrosterone sulfate (DHEAS) on the ecto-5'-nucleotidase activity in fresh clinical (VP60) and in long-term-grown (30236 ATCC) isolates of T. vaginalis. In vitro exposure to DHEAS and 17beta-estradiol did not induce any changes in adenosine monophosphate (AMP) hydrolysis in these isolates. The treatment of parasites in the presence of DHEAS (0.01-1.0 microM) for 2 h inhibited AMP hydrolysis in VP60 isolate, whereas there were no significant changes in nucleotide hydrolysis in the presence of 17beta-estradiol. DHEAS and 17beta-estradiol (0.01-1.0 microM) for 2 h inhibited AMP hydrolysis in 30236 isolate. The 12 treatment with 0.1 microM DHEAS inhibited AMP hydrolysis, whereas 17beta-estradiol did not alter the nucleotide hydrolysis in VP60 isolate. Our findings have shown that the complex effect of steroid hormones and their receptors on T. vaginalis may promote changes in ecto-5'-nucleotidase activity during exposure to these hormones.

show abstract

Adenosine is the primary precursor of all purine nucleotides in Trichomonas vaginalis

Cited by 37 publications

References 30 publications

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions

Identification of a Subversive Substrate of Trichomonas vaginalis Purine Nucleoside Phosphorylase and the Crystal Structure of the Enzyme-Substrate Complex

Steroid hormones alter AMP hydrolysis in intact trophozoites of Trichomonas vaginalis

Contact Info

Product

Resources

About