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.

journal_name

Glycobiology

journal_title

Glycobiology

authors

Li LX,Ashikov A,Liu H,Griffith CL,Bakker H,Doering TL

doi

10.1093/glycob/cww078

subject

Has Abstract

pub_date

2017-01-01 00:00:00

pages

87-98

issue

1

eissn

0959-6658

issn

1460-2423

pii

cww078

journal_volume

27

pub_type

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