Leishmania major CorA-like magnesium transporters play a critical role in parasite development and virulence

International Journal for Parasitology
Ying ZhuEmanuela Handman

Abstract

Establishment of infection by Leishmania depends on the transformation of the invading metacyclic promastigotes into the obligatory intracellular amastigotes, and their subsequent survival in the macrophage phagolysosome, which is low in magnesium. We show that two Leishmania major proteins designated MGT1 and MGT2, which play a critical role in these processes, belong to the two-transmembrane domain (2-TM-GxN) cation transporter family and share homology with the major bacterial magnesium transporter CorA. Although both are present in the endoplasmic reticulum throughout the life cycle of the parasite, MGT1 is more highly expressed in the infectious metacyclic parasites, while MGT2 is enriched in the immature procyclic stages. The two proteins, although predicted to be structurally similar, have features that suggest different regulatory or gating mechanisms. The two proteins may also be functionally distinct, since only MGT1 complements an Escherichia coli DeltaCorA mutant. In addition, deletion of one mgt1 allele from L. major led to increased virulence, while deletion of one allele of mgt2 resulted in slower growth and total loss of virulence in vitro and in vivo. This loss of virulence may be due to an impaired transformat...Continue Reading

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Citations

Oct 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Albert GuskovSaid Eshaghi
May 15, 2013·Journal of Proteomics·Raja Sekhar NirujogiAkhilesh Pandey
Jun 9, 2015·Biochimica Et Biophysica Acta·Robert M CleverleyStephen M Prince
Aug 21, 2013·Biochimica Et Biophysica Acta·Jian PayandehEmil F Pai
Dec 22, 2017·Emerging Topics in Life Sciences·Snezhana Akpunarlieva, Richard Burchmore
Jan 16, 2018·Journal of Proteome Research·Armando JardimChristoph H Borchers

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