De Novo Synthesis of Phosphatidylcholine Is Essential for the Promastigote But Not Amastigote Stage in Leishmania major

Phosphatidylcholine (PC) is the most abundant type of phospholipids in eukaryotes constituting ~30% of total lipids i

Editorial:Molecular Basis of Stage Conversion in Apicomplexan Parasites

No abstract available

Ethanolaminephosphate cytidylyltransferase is essential for survival, lipid homeostasis and stress tolerance in Leishmania major

Glycerophospholipids including phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are vital components of biological membranes. Trypanosomatid parasites of the genus Leishmania can acquire PE and PC via de novo synthesis and the uptake/remodeling of host lipids. In this study, we investigated the ethanolaminephosphate cytidylyltransferase (EPCT) in Leishmania major, which is the causative agent for cutaneous leishmaniasis. EPCT is a key enzyme in the ethanolamine branch of the Kennedy pathway which is responsible for the de novo synthesis of PE. Our results demonstrate that L. major EPCT is a cytosolic protein capable of catalyzing the formation of CDP-ethanolamine from ethanolamine-phosphate and cytidine triphosphate. Genetic manipulation experiments indicate that EPCT is essential in both the promastigote and amastigote stages of L. major as the chromosomal null mutants cannot survive without the episomal expression of EPCT. This differs from our previous findings on the choline branch of the Kennedy pathway (responsible for PC synthesis) which is required only in promastigotes but not amastigotes. While episomal EPCT expression does not affect promastigote proliferation under normal conditions, it leads to reduced production of ethanolamine plasmalogen or plasmenylethanolamine, the dominant PE subtype in Leishmania. In addition, parasites with episomal EPCT exhibit heightened sensitivity to acidic pH and starvation stress, and significant reduction in virulence. In summary, our investigation demonstrates that proper regulation of EPCT expression is crucial for PE synthesis, stress response, and survival of Leishmania parasites throughout their life cycle

The first Cryptosporidium meeting:a concerted effort to fight cryptosporidiosis

The first biennial Cryptosporidium meeting was held on 10–12 March 2024 in Philadelphia, PA, USA. The organizers, Dr Boris Striepen and Dr Christopher Hunter, welcomed more than 130 attendees to the University of Pennsylvania School of Veterinary Medicine. The meeting opened with a panel discussion featuring a diverse group of researchers, clinicians, non-profit and industry partners who offered unique insights into the problems of cryptosporidiosis. Seven research themed sessions (‘Impact of cryptosporidiosis’, ‘Population genetics’, ‘Genomics and new tools for research and translation’, ‘Parasite cell and developmental biology’, ‘Host–parasite interaction and immunity’, ‘Cryptosporidium metabolism and emerging targets’, and ‘Immunity to Cryptosporidium and vaccines’), as well as two poster sessions completed the meeting. A farewell dinner in the domed Asia gallery of the Penn Museum was organized for all the attendees. The meeting was graciously supported by the Bill and Melinda Gates Foundation, the Burroughs Wellcome Fund, Novartis, Zoetis, and several centers and departments of the University of Pennsylvania. In this TrendsTalk, we invited the session chairs to highlight the innovative research and discoveries presented during the inaugural Cryptosporidium meeting.<br/

The first Cryptosporidium meeting:a concerted effort to fight cryptosporidiosis

The first biennial Cryptosporidium meeting was held on 10–12 March 2024 in Philadelphia, PA, USA. The organizers, Dr Boris Striepen and Dr Christopher Hunter, welcomed more than 130 attendees to the University of Pennsylvania School of Veterinary Medicine. The meeting opened with a panel discussion featuring a diverse group of researchers, clinicians, non-profit and industry partners who offered unique insights into the problems of cryptosporidiosis. Seven research themed sessions (‘Impact of cryptosporidiosis’, ‘Population genetics’, ‘Genomics and new tools for research and translation’, ‘Parasite cell and developmental biology’, ‘Host–parasite interaction and immunity’, ‘Cryptosporidium metabolism and emerging targets’, and ‘Immunity to Cryptosporidium and vaccines’), as well as two poster sessions completed the meeting. A farewell dinner in the domed Asia gallery of the Penn Museum was organized for all the attendees. The meeting was graciously supported by the Bill and Melinda Gates Foundation, the Burroughs Wellcome Fund, Novartis, Zoetis, and several centers and departments of the University of Pennsylvania. In this TrendsTalk, we invited the session chairs to highlight the innovative research and discoveries presented during the inaugural Cryptosporidium meeting.<br/

Leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence

Leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. To understand the role of lipid metabolism in Leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. This study focuses on a putative phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in L. major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH is predominantly localized in the ER. While wild type L. major parasites are able to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the turnover of common glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF-AH is not required for the growth of L. major parasites in culture, or the production of GPI-anchored virulence factors. Nonetheless, it does play a key role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated virulence in BALB/c mice. In conclusion, these data suggest that Leishmania parasites possess a functional PAF-AH and the degradation of PAF or PAF-like lipids is an important step in infection