The regulation by iron of the synthesis of adhesins and cytoadherence levels in the protozoan Trichomonas vaginalis.

Abstract

SummaryLevels of adherence of Trichomonas vaginalis to epithelial cells was found to be modulated by iron . Cytoadherence values were greater than or equal to twofold higher for trichomonads grown in a complex cultivation medium supplemented with iron . This increase in adherence levels was specifically mediated by iron ; parasites cultured in a low-iron medium in the presence of salts other than iron were unresponsive to changes in adherence levels. Expression of the higher adherence property, by parasites grown first in low-iron medium followed by supplementation with iron, was a function of time, and the extent of cytoadherence was proportional to the concentration of iron added to the medium . Lactoferrin, an important iron source for trichomonads at the site of infection, elevated adherence of the parasite to epithelial cells, demonstrating the likely in vivo modulation of adherence by iron. The alteration of levels of adherence caused by iron was determined to be a reflection of gene expression of previously characterized trichomonad adhesins. Parasites grown under iron-replete conditions had higher quantities of surface-exposed adhesins, and this was a result of increased synthesis of adhesins. Actinomycin D and a-amanitin prevented expression of adhesin molecules, which resulted in decreased cytoadherence, showing that adhesin synthesis was dependent on gene transcription . Data indicated that genes encoding the four trichomonad adhesins are coordinately regulated by iron .Specificadherenceofmucosal pathogens to host cells leads to colonization, and this interaction is fundamental and prerequisite for infection and pathogenesis. Cytoadherence is an important mechanism by which infecting organisms overcome the flushing effect of mucosal secretions (1) . Trichomonas vaginalis is a flagellated protozoan responsible for one of the most common, world-wide sexually transmitted diseases, and the parasite affects mostly women. The emotional and economic consequences to all world societies caused by this protozoan are significant . This microorganism colonizes the vaginal epithelium by specific, receptor-ligand interactions (2) . Adherence to squamous vaginal epithelial cells by this parasite is mediated by four surface proteins (3) . The ability of T. vaginalis parasites to cytoadhere is the result of a complex cascade of events involving adhesin proteins (3) and proteinase activity (4) .These earlier studies were conducted with organisms grown in a complex, nutrient-rich medium different from that encountered by parasites in the vagina, a nutritional environment which itself is changing during the menstrual cycle . Recent continuous flow culture experiments demonstrated that T. vaginalis organisms were capable of altering several properties in response to varying culture environments (5) . In addition, growth and multiplication (6), and certain virulence traits of T. vaginalis, were found to be modulated by iron, which is an essential nutrient for this parasite (6, 7). This ability of pathogenic human trichomon...

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

“…Parasites were grown in trypticase/yeast extract/maltose medium supplemented with 10 % (v/v) heat-inactivated horse serum as described by Diamond (1957). Exponential-phase parasites were grown in high iron (250 mM ferrous sulfate) and in iron-depleted medium with 100 mM 2,29-dipyridyl (Sigma) (Lehker et al, 1991;Crouch & Alderete, 2001). …”

“…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). Tsai et al (2002) identified an iron-responsive promoter in the ap65-1 gene which could be involved in the transcriptional regulation of some of these genes.…”

Inducing Immune Protection Against Trichomonas vaginalis: A Novel Vaccine Approach to Prevent HIV Transmission

“…Another mechanism of interest is the availability of iron and its role in regulating immune evasion, and expression of adhesins and cysteine proteases (Lehker et al, 1991;Lehker & Alderete, 1992). Alternative pathway complement lysis allows destruction of trichomonads under low iron conditions assessed by Alderete et al (1995).…”

Development of Drug Resistance in Trichomonas vaginalis and its Overcoming with Natural Products

“…As a result, the pH increases and offers a better environment for invasion and growth of the parasite [22]. Menstrual blood also increases the pH and serves as iron supply to enhance the attachment of T. vaginalis [23]. Of particular relevance is the increased risk of human immunodeficiency virus (HIV) co-infection facilitated by local inflammation and microscopic breaches in mucosal barriers [24].…”