title: Cryptococcus neoformans UGT1 encodes a UDP-Galactose/UDP-GalNAc transporter.
abstract: Cryptococcus neoformans, an opportunistic fungal pathogen, produces a glycan capsule to evade the immune system during infection. This definitive virulence factor is composed mainly of complex polysaccharides, which are made in the secretory pathway by reactions that utilize activated nucleotide sugar precursors. Although the pathways that synthesize these precursors are known, the identity and the regulation of the nucleotide sugar transporters (NSTs) responsible for importing them into luminal organelles remain elusive. The UDP-galactose transporter, Ugt1, was initially identified by homology to known UGTs and glycan composition analysis of ugt1Δ mutants. However, sequence is an unreliable predictor of NST substrate specificity, cells may express multiple NSTs with overlapping specificities, and NSTs may transport multiple substrates. Determining NST activity thus requires biochemical demonstration of function. We showed that Ugt1 transports both UDP-galactose and UDP-N-acetylgalactosamine in vitro. Deletion of UGT1 resulted in growth and mating defects along with altered capsule and cellular morphology. The mutant was also phagocytosed more readily by macrophages than wild-type cells and cleared more quickly in vivo and in vitro, suggesting a mechanism for the lack of virulence observed in mouse models of infection.
authors: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors: Lucy X
authors: LX
authors: Li
authors: Department of Cellular Chemistry, Hannover Medical School, D-30625 Hannover, Germany.
authors: Angel
authors: A
authors: Ashikov
authors: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors: Hong
authors: H
authors: Liu
authors: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA.
authors: Cara L
authors: CL
authors: Griffith
authors: Department of Cellular Chemistry, Hannover Medical School, D-30625 Hannover, Germany.
authors: Hans
authors: H
authors: Bakker
authors: Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, 63110, USA doering@wustl.edu.
authors: Tamara L
authors: TL
authors: Doering
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001692:Biological Transport / Q000235:genetics; D003453:Cryptococcosis / Q000201:enzymology / Q000235:genetics*; D003455:Cryptococcus neoformans / Q000201:enzymology / Q000276:immunology* / Q000472:pathogenicity; D004195:Disease Models, Animal; D005690:Galactose / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000276:immunology*; D011134:Polysaccharides / Q000235:genetics / Q000276:immunology; D013379:Substrate Specificity; D014531:Uridine Diphosphate Galactose / Q000235:genetics / Q000276:immunology*; D000099237:UDP-Galactose Translocators
chemical_list: D005690:Galactose; D009004:Monosaccharide Transport Proteins; D011134:Polysaccharides; D014531:Uridine Diphosphate Galactose; D000099237:UDP-Galactose Translocators
keywords: Cryptococcus neoformans; UDP-GalNAc; UDP-galactose; nucleotide sugar transporters; polysaccharide capsule