Albuquerque-Wendt, Andreia, McCoy, Ciaran, Neish, Rachel et al. (8 more authors) (2025) TransLeish:Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen. Nature Communications. 299. ISSN 2041-1723
Abstract
For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L. mexicana transportome. A total of 312 protein components of small molecule carriers, ion channels and pumps were identified and targeted in a CRISPR-Cas9 gene deletion screen in the promastigote form, yielding 188 viable null mutants. Forty transporter deletions caused significant loss of fitness in macrophage and mouse infections. A striking example is the Vacuolar H+ ATPase (V-ATPase), which, unexpectedly, was dispensable for promastigote growth in vitro but essential for survival of the disease-causing amastigotes.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024. The Author(s). |
Keywords: | Animals,Mice,Gene Deletion,Macrophages/parasitology,CRISPR-Cas Systems,Protozoan Proteins/genetics,Membrane Transport Proteins/genetics,Leishmania mexicana/genetics,Vacuolar Proton-Translocating ATPases/genetics,Female,Mice, Inbred BALB C |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 03 Jan 2025 16:00 |
Last Modified: | 30 Jan 2025 00:10 |
Published Version: | https://doi.org/10.1038/s41467-024-55538-7 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/s41467-024-55538-7 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221309 |
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Description: TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen
Licence: CC-BY 2.5