Genetic Structure and Expression of the Surface Glycoprotein GP82, the Main Adhesin of Trypanosoma cruzi Metacyclic Trypomastigotes

Abstract

T. cruzi improves the likelihood of invading or adapting to the host through its capacity to present a large repertoire of surface molecules. The metacyclic stage-specific surface glycoprotein GP82 has been implicated in host cell invasion. GP82 is encoded by multiple genes from the trans-sialidase superfamily. GP82 shows a modular organization, with some variation of N-terminal region flanking a conserved central core where the binding sites to the mammalian cell and gastric mucin are located. The function of GP82 as adhesin in host cell invasion process could expose the protein to an intense conservative and selective pressure. GP82 is a GPI-anchored surface protein, synthesized as a 70 kDa precursor devoid of N-linked sugars. GPI-minus variants accumulate in the ER indicating that GPI anchor acts as a forward transport signal for progressing along the secretory pathway as suggested for T. cruzi mucins. It has been demonstrated that the expression of GP82 is constitutive and may be regulated at post-transcriptional level, for instance, at translational level and/or mRNA stabilization. GP82 mRNAs are mobilized to polysomes and consequently translated, but only in metacyclic trypomastigotes. Analysis of transgenic parasites indicates that the mechanism regulating GP82 expression involves multiple elements in the 3′UTR.

Molecular Characterization of a Novel Family of Trypanosoma cruzi Surface Membrane Proteins (TcSMP) Involved in Mammalian Host Cell Invasion

“…The presence of several initiation codons in the same reading frame is common among T . cruzi surface protein genes such as GP82 and GP90 [ 41 , 42 ].…”

Potential Drug Targets in the Pentose Phosphate Pathway of Trypanosomatids

“…Version: Postprint (identical content as published paper) This is a self-archived document from i3S -Instituto de Investigação e Inovação em Saúde in the University of Porto Open Repository For Open Access to more of our publications, please visit http://repositorio-aberto.up.pt/ A01/00 kDa), which contributes to parasite internalization [109]. Inside the cytoplasm of host cells trypomastigotes differentiate into amastigotes that replicate by binary fission.…”

Epidemiological Aspects of Chagas Disease - a Review

“…Thus, the metacyclic trypomastigotes are allowed to enter into skin lesions or into the conjunctiva; oral ingestion of food or drink contaminated with infected reduviid faeces also cause human infection [34]. Metacyclic trypomastigotes express a stage specific surface glycoprotein of 82 kDa (GP82), a major cell adhesion molecule, responsible in parasite internalization [35].…”

“…Benznidazole treatment of congenital infection is highly effective, with cure rates >90 % when instituted in the first few weeks of life [28]. The children of < 12 years of age can be treated with benznidazole (10 mg/kg/day) [35]. Other potentially beneficial drugs, such as allopurinol or itraconazole, do not have a high enough degree of clinical efficacy, as compared with nifurtimox or benznidazole; posaconazole is a promising drug, but expensive [61].…”