Date: 11 March 2026
Time: 14:00-16:00
Location: ZOOM & SALA FRAGA DE AZEVEDO
Leishmania parasites must adjust their physiology and nutrient acquisition to thrive in two very different hosts: the phlebotomine sand fly and the mammalian macrophage. Transporter proteins, which mediate the movement of solutes, ions, metabolites, and drugs across membranes, play a central role in this adaptation.
To uncover which transporters are critical for parasite viability and fitness, CRISPR/Cas9 was used to construct a library of over 300 barcoded deletion mutants targeting the complete set of solute transporters, ion pumps, and channels in L. mexicana. Approximately two-thirds of genes could be deleted without preventing growth of cultured promastigotes, while one-third appeared refractory to deletion, under these conditions. A minority of the viable mutants displayed dramatic reduction of growth rates in vitro.
When tested in more physiological environments – human iPSC-derived macrophages, mice, and sand flies – many additional mutants exhibited pronounced fitness defects. These included several mitochondrial transporters and proton pumps. Notably, the vacuolar H⁺ ATPase (V-ATPase) was dispensable for promastigote proliferation in axenic culture but proved essential for parasite survival inside macrophages, within mice, and in the sand fly gut.
Together, these findings highlight how parasite requirements differ between artificial culture and natural hosts. They emphasize the V-ATPase as a central regulator of homeostasis under in vivo conditions and identify a set of transporters that are essential for amastigote survival and therefore represent promising candidates for further functional investigation.
About Andreia Albuquerque Wendt
Andreia Wendt completed her PhD in 2018 at the Medical School of Hannover, Germany, focusing on the glycobiology of Apicomplexan parasites. She then joined Prof. Eva Gluenz’s lab in the UK and Switzerland, where she used CRISPR/Cas9 and BAR-seq approaches to characterize the transportome of Leishmania across its life cycle. This work revealed that the vacuolar proton ATPase pump is essential for parasite survival in both mammalian and vector hosts. Andreia Wendt is currently a project leader in a collaborative effort between Swiss Tropical and Public Health Institute, Allschwil, Switzerland (Swiss TPH), and Charles University, Czech Republic, developing novel transmission-blocking strategies against Leishmania. Her research explores the complex interactions between host, pathogen, and vector, aiming to inform innovative approaches for controlling and ultimately eradicating leishmaniases.
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