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.

The putrescine analogue 1,4-diamino-2-butanone affects polyamine synthesis, transport, ultrastructure and intracellular survival in Leishmania amazonensis

“…The putrescine analogue DAB has been tested in different micro-organisms (Calvo-Méndez et al, 1993;ArteagaNieto et al, 1996;Reis et al, 1999;Garcia et al, 2005;Menezes et al, 2006) and was effective against DFMOresistant parasites (Calvo-Méndez et al, 1993;Reis et al, 1999). DAB has also been shown to be a powerful ODC inhibitor in a number of organisms (Calvo-Méndez et al, 1993;Arteaga-Nieto et al, 1996).…”

Plasma Antibodies against Trichomonas vaginalis and Subsequent Risk of Prostate Cancer

“…Interestingly, spermine has been observed to inhibit prostatic carcinoma growth in vitro and in vivo (42), and lower concentrations of spermine have been observed in malignant prostate tissue than in normal or hyperplastic tissue (43), suggesting that spermine may be involved in prostate carcinogenesis. Finally, the fact that putrescine secretion by trichomonads contributes to a complex interplay between parasite and host cells is evidence of the intricate interrelationship that exists during infection (44).…”

Involvement of potD in Streptococcus pneumoniae Polyamine Transport and Pathogenesis

“…The concentrations of intracellular polyamines have been shown to influence the efficiency and fidelity of translation and to stabilize DNA, RNA, and various enzymes involved in both transcription and translation as well as to modulate the synthesis of various proteins at the translational level (31). The polyamine putrescine has been shown to restore virulence gene expression in the pathogen Shigella flexneri (10), to influence the formation of filaments in Candida albicans that are necessary for virulence in mouse models (16), and to be involved in host cell adherence by Trichomonas vaginalis (11). The data presented here show that the polyamine transport system encoded by potABCD influences the overall pathogenesis of Streptococcus pneumoniae within the murine host.…”