The differential expression of the Trichomonas vaginalis cysteine proteinase TVCP4 by iron at the protein synthesis level and the prediction of an iron-responsive element (IRE)-like stem-loop structure at the 5 0 -region of the T. vaginalis cysteine proteinase 4 gene (tvcp4) mRNA suggest a post-transcriptional mechanism of iron regulation in trichomonads mediated by an IRE/IRP-like system. Gel-shifting, UV cross-linking and competition experiments demonstrated that this IRE-like structure specifically bound to human iron regulatory protein-1. IRP-like cytoplasmic proteins that bound human ferritin IRE sequence transcripts at low-iron conditions were also found in trichomonads. Thus, a post-transcriptional regulatory mechanism by iron for tvcp4 mediated by IRE/IRP-like interactions was found.
Trichomonas vaginalis is the causative agent of trichomoniasis, one of the most common sexually transmitted diseases in humans. This protozoan has multiple proteinases that are mainly of the cysteine proteinase (CP) type, some of which are known to be involved in the parasite's virulence. Here, a novel T. vaginalis CP-encoding gene, tvcp12, was identified and characterized. tvcp12 is 948 bp long and encodes a predicted 34·4 kDa protein that has the characteristics of the papain-like CP family. TvCP12 does not appear to have a signal peptide, suggesting that this is a cytoplasmic CP. By Southern blot assays, the tvcp12 gene was found as a single copy in the T. vaginalis genome. Remarkably, Northern blot experiments showed a single transcript band of ∼1·3 kb in the mRNA obtained from parasites grown in low iron conditions and no transcript was observed in the mRNA from parasites grown in high iron conditions. By RT-PCR assays, a 270 bp band was amplified from the cDNA of parasites grown in low iron medium, which was very faint when cDNA from parasites grown in high iron conditions was used. Transcripts of the 3′ region obtained in both iron conditions presented differences in their poly(A) tail length. These data suggest that tvcp12 is another gene that is negatively regulated by iron and that the length of the poly(A) tail may be one of the factors involved in the iron-modulated protein expression.
Entamoeba histolytica is a human parasite that causes amoebiasis, a disease that affects the colon and liver and is prevalent worldwide. This protozoan requires a high concentration of iron to survive and reproduce. Iron modulates the expression of parasite virulence factors, including hemoglobinases, hemoglobin-binding proteins and cysteine proteases, as well as proteins related to the amoebic cytoskeleton. This review summarizes the virulence factors that are affected by iron, resulting in upregulation or downregulation of E. histolytica genes. This review also discusses the functionality of iron in the mechanisms of pathogenesis.
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