Lactate Dehydrogenase Is Associated with the Parasitophorous Vacuole Membrane and Is a Potential Target for Developing Therapeutics

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Cryptosporidians are unique among the apicomplexans in regards to their parasitic life style (e.g., they are intracellular, but undergo extracytoplasmic development within a host membrane-derived structure termed parasitophorous vacuole membrane, PVM) and their metabolism (e.g., they are incapable of de novo nutrient synthesis and rely on glycolysis for the synthesis of ATP). We discovered that the Cryptosporidium parvum bacterial-type L-lactate dehydrogenase (CpLDH) enzyme is cytosolic during the parasite’s motile, extracellular, stages (sporozoites and merozoites), but becomes associated with the PVM during intracellular development, indicating the involvement of the PVM in lactate fermentation. We also observed that micromolar concentrations of the LDH inhibitors gossypol and FX11 inhibit both CpLDH activity and the growth of C. parvum in vitro, suggesting that CpLDH is a potential target for the development of anti-cryptosporidial therapeutics.

Vyšlo v časopise: Lactate Dehydrogenase Is Associated with the Parasitophorous Vacuole Membrane and Is a Potential Target for Developing Therapeutics. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005250
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005250

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