Compartmentalization of glycolytic enzymes in glycosomes is vital in trypanosomatid parasites. Retention of these enzymes in the cytosol induces sugar toxicity and accumulation of intermediate metabolites, notably the hexokinase product glucose-6-phosphate. However, the role of hexokinase in sugar mediated toxicity remains unexplored. We have generated Leishmania donovani transfectants expressing a catalytically active cytosolic mutant of hexokinase. In the presence of glucose, these transfectants exhibited toxicity during log and stationary phases of growth. These results suggest that targeting of hexokinase to the glycosome is required to prevent uncontrolled and cytotoxic glucose phosphorylation in L. donovani parasites.
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http://dx.doi.org/10.1016/j.molbiopara.2009.11.002 | DOI Listing |
BMC Infect Dis
January 2025
Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.
Background: Visceral leishmaniasis is endemic in Ethiopia and caused by Leishmania donovani. Although the disease manifests with significant clinical variability, a substantial number of individuals are asymptomatic. These individuals can serve as reservoirs, complicating control efforts.
View Article and Find Full Text PDFExp Parasitol
January 2025
Department of Biotechnology, Savitribai Phule Pune University, 411007, Pune, India. Electronic address:
Visceral leishmaniasis (VL) is an opportunistic infection in HIV patients with higher relapse and mortality rate. The number of HIV-VL patients is comparatively higher in areas where both infections are endemic. However, the conventional chemotherapeutic agents have limited success due to drug toxicity, efficacy variance and overall cost of treatment.
View Article and Find Full Text PDFCell Biol Int
January 2025
Laboratory of Leishmaniasis, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Leishmaniases affect millions of people around the world, caused by Leishmania parasites. Leishmania are transmitted by female sandflies from Phlebotominae subfamily during their blood meals. In mammals, promastigotes are phagocytosed mainly by macrophages, differentiate into amastigotes and multiply.
View Article and Find Full Text PDFPLoS Negl Trop Dis
December 2024
Genômica Funcional de Parasitos, Instituto René Rachou-Oswaldo Cruz Foundation, Belo Horizonte, Minas Gerais, Brazil.
Background: Visceral leishmaniasis (VL) is an infectious parasitic disease caused by the species Leishmania (Leishmania) infantum in the Mediterranean Basin, the Middle East, Central Asia, South America, and Central America, and Leishmania (Leishmania) donovani in Asia and Africa. VL represents the most severe and systemic form of the disease and is fatal if left untreated. Vaccines based on chimeric or multiepitope antigens hold significant potential to induce a highly effective and long-lasting immune response against infections by these parasites.
View Article and Find Full Text PDFACS Infect Dis
January 2025
Centre of Experimental Medicine and Surgery, Institute of Medical Sciences Banaras Hindu University, Varanasi-221005, U.P., India.
Protozoan parasite infections, particularly leishmaniasis, present significant public health challenges in tropical and subtropical regions, affecting socio-economic status and growth. Despite advancements in immunology, effective vaccines remain vague, leaving drug treatments as the primary intervention. However, existing medications face limitations, such as toxicity and the rise of drug-resistant parasites.
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