Iron regulates growth of Trichomonas vaginalis and the expression of immunogenic trichomonad proteins

Abstract

Iron is an essential nutrient for Trichomonas vaginalis and is acquired via highly specific receptor-mediated mechanisms from the host. Responses of T. vaginalis to conditions of iron limitation or iron excess were analysed in order to determine whether iron levels in the growth medium regulate certain properties of the parasite. When compared with organisms grown in excess iron, iron limitation resulted in greater than or equal to 80% lower rates of protein synthesis and greater than or equal to 3-fold decreases in cell densities. These parasites also exhibited generation times of approximately 10 hours, 2.5-fold longer than organisms grown in the usual complex medium. Iron-restricted growth also resulted in increased binding of lactoferrin by trichomonads, which paralleled elevated expression of the lactoferrin-binding receptor protein having a relative molecular mass of 136,000 daltons (136 kDa). A Mr 126 kDa protein was concomitantly repressed in low-iron-grown parasites. The greater amounts of lactoferrin bound by iron-depleted T. vaginalis organisms corresponded with both the expression of additional receptors onto trichomonal surfaces and increased affinity of the receptor for the lactoferrin molecule. Finally, immunoblot analysis of parasites grown under high- and low-iron conditions using sera from patients with trichomoniasis further revealed the synthesis by T. vaginalis of at least 19 iron-regulated immunogens, and patients' sera also detected the lactoferrin receptor. These data not only show the overall importance of iron to the biology of this protozoan, but illustrate the in vivo iron modulation of gene expression of the biofunctional lactoferrin receptor and other immunogens.

Trichomonas vaginalis perturbs the junctional complex in epithelial cells

“…As observed in the present work, a decrease in the expression of this protein was also related to a decrease in the adhesion rate supporting the idea that iron plays an important modulator effect on the parasite adhesion capacity, as previously suggested [18]. Although few changes in the localization and organization of junctional complex proteins were observed, it does not exclude that functional changes take place after interaction of T. vaginalis with Caco-2 cells.…”

“…These proteins interact with host cells via ligand-receptor-type interactions [17]. Furthermore, it has been reported that transcription and expression of genes coding for these proteins are greatly influenced by iron concentration in the medium where the protozoan was cultivated [18][19][20]. Pathogenicity is also influenced by cellular contact between pathogens and the epithelial cells, culminating in disturbance of the junctional complex [14,[21][22][23].…”

tvcp12: a novel Trichomonas vaginalis cathepsin L-like cysteine proteinase-encoding gene

“…The tvcp12 gene is iron-regulated; this is not surprising, because it has been established that different iron concentrations in the medium induce expression of different genes (Lehker & Alderete, 1992). The flp1 and flp2 genes of T. vaginalis, which encode proteins with homology to fibronectin, are induced under low iron growth conditions (Crouch & Alderete, 2001), whereas ap65 and the ap51 and ap33 genes are overexpressed in high iron concentration media Engbring et al, 1996;Alderete et al, 1998).…”

“…Iron modulates the expression of distinct T. vaginalis genes (Alderete et al, , 1998Engbring et al, 1996;Crouch & Alderete, 2001;Lehker & Alderete, 1992). To determine the effect of iron on tvcp12 transcription, trichomonads were grown under iron-replete and iron-depleted conditions Crouch & Alderete, 2001).…”

“…In trichomonads, iron is acquired from the host via highly specific receptor-mediated mechanisms (Peterson & Alderete, 1984;Lehker et al, 1990;Lehker & Alderete, 1992). In addition, iron controls the expression of hydrogenosomal proteins such as pyruvate : ferredoxin oxidoreductase and ferredoxin (Gorrell, 1985), and virulence genes, such as those encoding some of the T. vaginalis adhesin proteins (Lehker et al, 1991;Engbring et al, 1996;Alderete et al, 1998;García et al, 2003).…”