Identification and characterisation of UDP-galactofuranose transporter from the human pathogens Leishmania major and Aspergillus fumigatus

点击翻译按钮获取中文摘要

The sugar D-galactofuranose (Galf) is an unusual form of galactose, present at the cell surface of many pathogenic organisms including bacteria, fungi and protozoa, but absent from mammals. Galf being essential for survival or virulence of various bacteria, the enzymes involved in its metabolic pathways are viable targets for the development of new antibacterial drugs. We recently identified the first eukaryotic enzyme involved in Galf biosynthesis, the UDP-galactopyranose mutase. Our current studies demonstrate its contribution to the pathogenicity of Leishmania major and Aspergillus fumigatus providing encouraging results for the chemotherapeutical potential of Galf metabolism in eukaryotes. We now wish to identify and characterise another key player of Galf metabolism: the UDP-Galf transporter. Nucleotide sugar transporters are structurally conserved and can be readily identified from genome databases; however their substrate specificity cannot be predicted. Our approach will involve the selection of candidate nucleotide sugar transporter genes and their systematic deletion in the fungus Aspergillus fumigatus. The desired mutant can then be used for the identification of Leishmania major UDP-Galf transporter. With this proposal, we wish to unravel further Galf metabolism in eukaryotes.