title: Trichomonas vaginalis polyamine metabolism is linked to host cell adherence and cytotoxicity.
abstract: 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.
authors.affiliation: Department Microbiology, UTHSCSA, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900, USA.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Garcia
authors.forename: M
authors.initials: M
authors.lastname: Benchimol
authors.forename: J F
authors.initials: JF
authors.lastname: Alderete
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000469:parasitology / Q000473:pathology; D005260:Female; D006801:Humans; D011073:Polyamines / Q000378:metabolism*; D011700:Putrescine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D014246:Trichomonas vaginalis / Q000187:drug effects / Q000378:metabolism / Q000472:pathogenicity* / Q000502:physiology*; D014621:Vagina / Q000166:cytology* / Q000469:parasitology* / Q000473:pathology; D014774:Virulence
chemical_list: D011073:Polyamines; C014458:1,4-diaminobutanone; D011700:Putrescine