Enolase: A Key Player in the Metabolism and a Probable Virulence Factor of Trypanosomatid Parasites—Perspectives for Its Use as a Therapeutic Target

Abstract

Glycolysis and glyconeogenesis play crucial roles in the ATP supply and synthesis of glycoconjugates, important for the viability and virulence, respectively, of the human-pathogenic stages of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. These pathways are, therefore, candidate targets for antiparasite drugs. The glycolytic/gluconeogenic enzyme enolase is generally highly conserved, with similar overall fold and identical catalytic residues in all organisms. Nonetheless, potentially important differences exist between the trypanosomatid and host enzymes, with three unique, reactive residues close to the active site of the former that might be exploited for the development of new drugs. In addition, enolase is found both in the secretome and in association with the surface of Leishmania spp. where it probably functions as plasminogen receptor, playing a role in the parasite's invasiveness and virulence, a function possibly also present in the other trypanosomatids. This location and possible function of enolase offer additional perspectives for both drug discovery and vaccination.

Exploiting death: apoptotic immunity in microbial pathogenesis

“…This is consistent with the lack of association of glycosomal and non-glycosomal enzymes reported in Trypanosoma cruzi, in which the externalization of extraglycosomal enolase 50 appears to occur without the involvement of intraglycosomal triosephosphate isomerase. 54 Beyond the evolutionary significance of enolase externalization, this may suggest that other glycolytic enzyme molecules are dispensable for the triggering of IAI.…”

“…50,51 (The functional significance of plasminogen binding with respect to Leishmania pathogenesis has not been established definitively. 52 ) Proteomic analysis indicates that .…”

“…53 As in the case of glycolytic enzyme molecule exposure associated with apoptosis, externalized Leishmania enolase has no enzymatic activity. 12,50,53 In this case, enolase appears to be regulated by posttranslational modification (dependent on oligopeptidase B 53 ).…”

Role of Δ1-Pyrroline-5-Carboxylate Dehydrogenase Supports Mitochondrial Metabolism and Host-Cell Invasion of Trypanosoma cruzi

“…T. brucei responds to citrate exposure at the initiation of its life cycle during transmission to the tsetse fly (98). Furthermore, in Leishmania parasites, enolase and arginase represent examples of enzymes that participate in the infection process or pathogenesis (99,100).…”

Expression of Eleven Egg Performance-associated Genes in the Ovary of Zi Geese <i>Anser anser domestica</i>

“…This paper described the relative expression profiles of eleven eggperformance associated genes in ovaries of both pre-laying and laying Zi geese. ENO1 is a key enzyme in the glycolytic pathway which catalyzes the reversible conversion of D-2-phosphoglycerate into phosphoenol-pyruvate in the second half of the glycolytic pathway (Avilán et al, 2011). Recent studies have revealed that ENO1 can be detected in many prokaryotic and eukaryotic cells, and localized in cytoplasm, cell surface and nucleus of various mammalian cells to possibly mediate distinct functions (Liu et al, 2007).…”