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The glucose sensor-like protein Hxs1 is a high-affinity glucose transporter and required for virulence in Cryptococcus neoformans
- Source :
- PLoS ONE, Vol 8, Iss 5, p e64239 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Cryptococcus is a major fungal pathogen that frequently causes systemic infection in patients with compromised immunity. Glucose, an important signal molecule and the preferred carbon source for Cryptococcus, plays a critical role in fungal development and virulence. Cryptococcus contains more than 50 genes sharing high sequence homology with hexose transporters in Saccharomyces cerevisiae. However, there is no report on their function in glucose sensing or transport. In this study, we investigated two hexose transporter-like proteins (Hxs1 and Hxs2) in Cryptococcus that share the highest sequence identity with the glucose sensors Snf3 and Rgt2 in S. cerevisiae. The expression of HXS1 is repressed by high glucose, while the HXS2 expression is not regulated by glucose. Functional studies showed that Hxs1 is required for fungal resistance to oxidative stress and fungal virulence. The hxs1Δ mutant exhibited a significant reduction in glucose uptake activity, indicating that Hxs1 is required for glucose uptake. Heterologous expression of Cryptococcus HXS1 rendered the S. cerevisiae mutant lacking all 20 hexose transporters a high glucose uptake activity, demonstrating that Hxs1 functions as a glucose transporter. Heterologous expression of HXS1 in the snf3Δ rgt2Δ double mutant did not complement its growth in YPD medium containing the respiration inhibitor antimycin A, suggesting that Hxs1 may not function as a glucose sensor. Taken together, our results demonstrate that Hxs1 is a high-affinity glucose transporter and required for fungal virulence.
- Subjects :
- Snf3
Saccharomyces cerevisiae Proteins
Monosaccharide Transport Proteins
Glucose uptake
Cryptococcus
Glucose Transport Proteins, Facilitative
Virulence
Antimycin A
lcsh:Medicine
Mycology
Pathogenesis
Plant Science
Saccharomyces cerevisiae
Biochemistry
Microbiology
Fungal Proteins
Gene Expression Regulation, Fungal
Fungal Biochemistry
lcsh:Science
Biology
Microbial Pathogens
Cryptococcus neoformans
Fungal protein
Multidisciplinary
biology
Sequence Homology, Amino Acid
lcsh:R
Glucose transporter
Fungi
Botany
Fungal Diseases
Biological Transport
Cryptococcosis
biology.organism_classification
Oxidative Stress
Metabolism
Infectious Diseases
Glucose
Mutation
Medicine
lcsh:Q
Heterologous expression
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 8
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....d4f66413653d84962bc6b99b04f949d5