<i>Cryptococcus neoformans UGT1</i>encodes a UDP-Galactose/UDP-GalNAc transporter

Li, Lucy X.; Ashikov, Angel; Liu, Hong; Griffith, Cara L.; Bakker, Hans; Doering, Tamara L.

doi:10.1093/glycob/cww078

Cited by 21 publications

(20 citation statements)

References 76 publications

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“…To our knowledge galactosamine has not been previously detected in C. neoformans cell wall or capsule, although one study identified a UGT1 (UDP-galactose transporter) gene responsible for the transport of both UDP-galactose and UDP-galactosamine in vitro (Li et al, 2017). This finding together with our observation suggest the presence of both galactose and galactosamine in C. neoformans polysaccharides.…”

Section: Discussionmentioning

confidence: 99%

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

et al. 2018

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Cryptococcus neoformans is a human fungal pathogen that often causes infections in immunocompromised individuals. Upon inhalation into the lungs C. neoformans differentiates into cells with altered size and morphology, including production of large titan cells. Titan cells possess thickened cell wall and dense, cross-linked capsule when compared to in vitro grown cells. In addition, titan cells have increased cell wall chitin that is associated with a detrimental anti-inflammatory immune response. Here we examined the cell wall and capsule composition of in vitro, in vivo typical-sized and in vivo titan cells using High Performance Liquid Chromatography (HPLC). The monomer composition of cell wall polysaccharides showed that in vivo C. neoformans cells contained more glucosamine and less glucose than in vitro cells, suggesting alteration in abundance of both chitin and glucans, respectively. Low levels of galactosamine were also detected in carbohydrates from both in vivo and vitro cells. Within the in vivo cell population, differences in the proportions of cell wall and capsule monomers between typical and titan cells were also observed. Taken together, these results demonstrate that C. neoformans reshapes its cell wall and capsule composition during infection. These cell wall and capsule alterations likely help C. neoformans escape recognition by, and allow modulation of, the host immune system.

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Section: Discussionmentioning

confidence: 99%

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

et al. 2018

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“…It is clear that interaction with the host is influenced by both capsule secretion and composition [23][24][25]. Newly synthesized polysaccharide is added to the existing capsule via secretion of extracellular vesicles [24,25]]. Deletion of the flippase Apt1 alters Golgi morphology (where capsule biosynthesis occurs) and limits growth of the capsule in the mouse lung but not liquid culture [26].…”

Section: Host Condition Dependent Changes In C Neoformansmentioning

confidence: 99%

The cause and effect of Cryptococcus interactions with the host

Ballou

Johnston

2017

Current Opinion in Microbiology

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Upon Cryptococcus neoformans infection of the host lung, the fungus enters a nutrient poor environment and must adapt to a variety of host-specific stress conditions (temperature, nutrient limitation, pH, CO). Fungal spores enter this milieu with limited nutritional reserves, germinate, and begin proliferating by budding as yeast. Although relatively little is known about the initial stages of infection, recent work has characterized changes that occur upon germination. This program and subsequent yeast-phase proliferation progress in a dynamic environment as host nutrient immunity responds to the infection via toxic accumulation or sequestration of essential micronutrients and innate immune cells are recruited to the site of infection. Adaptation to the host environment and evasion of the immune response through pathogenicity factor expression allows proliferation and dissemination to multiple sites throughout the body, including, most significantly for human disease, the central nervous system. Here we will discuss recent insights into mechanisms underlying C. neoformans interactions with the host during infection.

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“…The charged donors enter the luminal space via nucleotide sugar transporters (NSTs), which exchange activated sugars for the corresponding nucleoside monophosphates [ 18 , 19 ]. NSTs thus mediate a limiting step in glycan biosynthesis, and are consequently required for cryptococcal viability and pathogenicity [ 20 – 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…In prior work, protein structure predictions and homology facilitated identification of the cryptococcal NSTs responsible for GDP-Man [ 21 , 30 ] and UDP-Gal [ 20 , 22 ] transport. We have now used product analysis and mass spectrometry based assays to discover Uxt1 and Uxt2, which both transport UDP-Xyl and UDP-Gal f although they exhibit distinct subcellular localization, expression patterns, and kinetic parameters.…”

Section: Introductionmentioning

confidence: 99%

Xylose donor transport is critical for fungal virulence

Rautengarten

Heazlewood

et al. 2018

PLoS Pathog

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Cryptococcus neoformans, an AIDS-defining opportunistic pathogen, is the leading cause of fungal meningitis worldwide and is responsible for hundreds of thousands of deaths annually. Cryptococcal glycans are required for fungal survival in the host and for pathogenesis. Most glycans are made in the secretory pathway, although the activated precursors for their synthesis, nucleotide sugars, are made primarily in the cytosol. Nucleotide sugar transporters are membrane proteins that solve this topological problem, by exchanging nucleotide sugars for the corresponding nucleoside phosphates. The major virulence factor of C. neoformans is an anti-phagocytic polysaccharide capsule that is displayed on the cell surface; capsule polysaccharides are also shed from the cell and impede the host immune response. Xylose, a neutral monosaccharide that is absent from model yeast, is a significant capsule component. Here we show that Uxt1 and Uxt2 are both transporters specific for the xylose donor, UDP-xylose, although they exhibit distinct subcellular localization, expression patterns, and kinetic parameters. Both proteins also transport the galactofuranose donor, UDP-galactofuranose. We further show that Uxt1 and Uxt2 are required for xylose incorporation into capsule and protein; they are also necessary for C. neoformans to cause disease in mice, although surprisingly not for fungal viability in the context of infection. These findings provide a starting point for deciphering the substrate specificity of an important class of transporters, elucidate a synthetic pathway that may be productively targeted for therapy, and contribute to our understanding of fundamental glycobiology.

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Cryptococcus neoformans UGT1encodes a UDP-Galactose/UDP-GalNAc transporter

Cited by 21 publications

References 76 publications

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

Titan cell production in Cryptococcus neoformans reshapes the cell wall and capsule composition during infection

The cause and effect of Cryptococcus interactions with the host

Xylose donor transport is critical for fungal virulence

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