Kharon1 null mutants of Leishmania mexicana are avirulent in mice and exhibit a cytokinesis defect within macrophages.
In a variety of eukaryotes, flagella play important roles both in motility and as sensory organelles that monitor the extracellular environment. In the parasitic protozoan Leishmania mexicana, one glucose transporter isoform, LmxGT1, is targeted selectively to the flagellar membrane where it appears to play a role in glucose sensing. Trafficking of LmxGT1 to the flagellar membrane is dependent upon interaction with the KHARON1 protein that is located at the base of the flagellar axoneme. Remarkably, while Δkharon1 null mutants are viable as insect stage promastigotes, they are unable to survive as amastigotes inside host macrophages. Although Δkharon1 promastigotes enter macrophages and transform into amastigotes, these intracellular parasites are unable to execute cytokinesis and form multinucleate cells before dying. Notably, extracellular axenic amastigotes of Δkharon1 mutants replicate and divide normally, indicating a defect in the mutants that is only exhibited in the intra-macrophage environment. Although the flagella of Δkharon1 amastigotes adhere to the phagolysomal membrane of host macrophages, the morphology of the mutant flagella is often distorted. Additionally, these null mutants are completely avirulent following injection into BALB/c mice, underscoring the critical role of the KHARON1 protein for viability of intracellular amastigotes and disease in the animal model of leishmaniasis.
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
Khoa D
KD
Tran
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
Danielle P
DP
Vieira
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
Marco A
MA
Sanchez
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Jessica
J
Valli
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Eva
E
Gluenz
Department of Molecular Microbiology & Immunology, Oregon Health & Science University, Portland, Oregon, United States of America.
Scott M
SM
Landfear
D000818:Animals; D048749:Cytokinesis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics*; D005407:Flagella / Q000235:genetics* / Q000469:parasitology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D007894:Leishmania mexicana / Q000235:genetics / Q000472:pathogenicity; D007896:Leishmaniasis / Q000235:genetics* / Q000469:parasitology / Q000473:pathology; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D009154:Mutation; D015800:Protozoan Proteins / Q000235:genetics*
D003598:Cytoskeletal Proteins; D051246:Glucose Transport Proteins, Facilitative; D015800:Protozoan Proteins