Evidence that intracellular beta 1-2 mannan is a virulence factor in Leishmania parasites
AuthorRalton, JE; Naderer, T; Piraino, HL; Bashtannyk, TA; Callaghan, JM; McConville, MJ
Source TitleJOURNAL OF BIOLOGICAL CHEMISTRY
PublisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
University of Melbourne Author/sRalton, Julie; McConville, Malcolm; CALLAGHAN, JUDITH; NADERER, THOMAS; PIRAINO, HELENA LOUISE; Puhalovich, Tanya
AffiliationBiochemistry And Molecular Biology
Document TypeJournal Article
CitationsRalton, J. E., Naderer, T., Piraino, H. L., Bashtannyk, T. A., Callaghan, J. M. & McConville, M. J. (2003). Evidence that intracellular beta 1-2 mannan is a virulence factor in Leishmania parasites. JOURNAL OF BIOLOGICAL CHEMISTRY, 278 (42), pp.40757-40763. https://doi.org/10.1074/jbc.M307660200.
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C1 - Journal Articles Refereed
The protozoan parasite Leishmania mexicana proliferates within macrophage phagolysosomes in the mammalian host. In this study we provide evidence that a novel class of intracellular beta1-2 mannan oligosaccharides is important for parasite survival in host macrophages. Mannan (degree of polymerization 4-40) is expressed at low levels in non-pathogenic promastigote stages but constitutes 80 and 90% of the cellular carbohydrate in the two developmental stages that infect macrophages, non-dividing promastigotes, and lesion-derived amastigotes, respectively. Mannan is catabolized when parasites are starved of glucose, suggesting a reserve function, and developmental stages having low mannan levels or L. mexicana GDPMP mutants lacking all mannose molecules are highly sensitive to glucose starvation. Environmental stresses, such as mild heat shock or the heat shock protein-90 inhibitor, geldanamycin, that trigger the differentiation of promastigotes to amastigotes, result in a 10-25-fold increase in mannan levels. Developmental stages with low mannan levels or L. mexicana mutants lacking mannan do not survive heat shock and are unable to differentiate to amastigotes or infect macrophages in vitro. In contrast, a L. mexicana mutant deficient only in components of the mannose-rich surface glycocalyx differentiates normally and infects macrophages in vitro. Collectively, these data provide strong evidence that mannan accumulation is important for parasite differentiation and survival in macrophages.
KeywordsBiochemistry and Cell Biology not elsewhere classified ; Biological Sciences
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