15043861

pubmed:Citation

5

Trichomonas vaginalis is a protozoan responsible for the number one, non-viral sexually transmitted disease. Surface proteins (AP65, AP51, AP33 and AP23) mediate adherence to vaginal epithelial cells (VECs). Iron increases growth of trichomonads and synthesis and surface placement of adhesins. We observed by immunofluorescence using monoclonal antibody (mAb) 12G4 the placement of AP65 on surfaces of trichomonads supplemented with hemoglobin or hemin as a source of iron. We, therefore, tested the hypothesis that heme-bound iron is an alternative source of iron important to trichomonal growth and regulation of expression of the adhesin genes. Here we show that the inhibition of parasite growth by the iron chelator 2,2-dipyridal is rescued by hemoglobin or hemin, but not protoporphyrin IX. Importantly, trichomonads grown in iron-limiting medium supplemented with free iron, hemoglobin and hemin had elevated levels of ap65 transcript that were 12.6-, 12.3- and 9.2-fold higher, respectively, than low-iron organisms, as determined by RT-PCR. Similarly, the amounts of AP65 were 8.9-, 11.2-, and 4.8-fold higher in parasites grown in free iron, hemoglobin and hemin, respectively, than organisms in low-iron medium. The heme-iron-regulated AP65 increased adherence of parasites to immortalized VECs. Not surprisingly, parasites pretreated with anti-AP65 serum IgG had decreased adherence compared to organisms incubated with prebleed serum IgG. These data illustrate that heme-bound iron is a source of iron similar to lactoferrin. This work extends our findings about the multiple sources of iron for regulating virulence genes of T. vaginalis.

eng

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MEDLINE

0882-4010

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NLM

263-71

pubmed-meshheading:15043861-2,2'-Dipyridyl, pubmed-meshheading:15043861-Animals, pubmed-meshheading:15043861-Antibodies, Protozoan, pubmed-meshheading:15043861-Cell Adhesion, pubmed-meshheading:15043861-Cell Adhesion Molecules, pubmed-meshheading:15043861-Chelating Agents, pubmed-meshheading:15043861-Epithelial Cells, pubmed-meshheading:15043861-Gene Expression, pubmed-meshheading:15043861-Growth Inhibitors, pubmed-meshheading:15043861-Heme, pubmed-meshheading:15043861-Hemin, pubmed-meshheading:15043861-Hemoglobins, pubmed-meshheading:15043861-Humans, pubmed-meshheading:15043861-Iron, pubmed-meshheading:15043861-Membrane Proteins, pubmed-meshheading:15043861-Protoporphyrins, pubmed-meshheading:15043861-Protozoan Proteins, pubmed-meshheading:15043861-RNA, Messenger, pubmed-meshheading:15043861-RNA, Protozoan, pubmed-meshheading:15043861-Trichomonas vaginalis

Heme-iron increases levels of AP65-mediated adherence by Trichomonas vaginalis.

Journal Article, Research Support, U.S. Gov't, P.H.S.