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Targeted gene deletion of leishmania major UDP-galactopyranose mutase leads to attenuated virulence

Kleczka, B. and Lamerz, A.C. and van Zandbergen, G. and Wiese, M. (2007) Targeted gene deletion of leishmania major UDP-galactopyranose mutase leads to attenuated virulence. Journal of Biological Chemistry, VOL. 282 (14). pp. 10498-10505. ISSN Print ISSN 0021-9258; Online ISSN 1083-351X

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Abstract

Considering the high incidence of galactofuranose (Galf) in pathogens and its absence from higher eukaryotes, the enzymes involved in the biosynthesis of this unusual monosaccharide appear as attractive drug targets. However, although the importance of Galf in bacterial survival or pathogenesis is established, its role in eukaryotic pathogens is still undefined. Recently, we reported the identification and characterization of the first eukaryotic UDP-galactopyranose mutases. This enzyme holds a central role in Galf metabolism by providing UDP-Galf to all galactofuranosyltransferases. In this work, the therapeutical potential of Galf metabolism in Leishmania major was hence evaluated by targeted replacement of the GLF gene encoding UDP-galactopyranose mutase. In L. major, Galf is present in the membrane anchor of the lipophosphoglycan (LPG) and in glycoinositolphospholipids. Accordingly, the generated glfmutant is deficient in LPG backbone and expresses truncated glycoinositolphospholipids. These structural changes do not influence the in vitro growth of the parasite but lead to an attenuation of virulence comparable with that observed with a mutant exclusively deficient in LPG.

Item type: Article
ID code: 9176
Keywords: galactofuranose, pathogens, biosynthesis, bacterial survival, pathogenesis, eukaryotic UDP-galactopyranose mutases, Leishmania major, GLF gene encoding, glycoinositolphospholipids, LPG, Science (General), Medicine (General), Pathology, Physiology, Biochemistry, Cell Biology, Molecular Biology
Subjects: Science > Science (General)
Medicine > Medicine (General)
Medicine > Pathology
Science > Physiology
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
Depositing user: Strathprints Administrator
Date Deposited: 04 Dec 2009 19:12
Last modified: 04 Sep 2014 21:14
URI: http://strathprints.strath.ac.uk/id/eprint/9176

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