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A Novel Small Molecule Methyltransferase Is Important for Virulence in Candida albicans
- Source :
- ACS Chemical Biology. 8:2785-2793
- Publication Year :
- 2013
- Publisher :
- American Chemical Society (ACS), 2013.
-
Abstract
- Candida albicans is an opportunistic pathogen capable of causing life-threatening infections in immunocompromised individuals. Despite its significant health impact, our understanding of C. albicans pathogenicity is limited, particularly at the molecular level. One of the largely understudied enzyme families in C. albicans is small molecule AdoMet-dependent methyltransferases (smMTases), which are important for maintenance of cellular homeostasis by clearing toxic chemicals, generating novel cellular intermediates and regulating intra- and interspecies interactions. Putative smMTase orf19.633 has little homology to any known protein and was previously identified based on its ability to functionally complement a baker’s yeast crg1 mutant in response to protein phosphatase inhibitor cantharidin. In this study, we demonstrated that C. albicans Crg1 (CaCrg1) is a bona fide smMTase that interacts with the toxin in vitro and in vivo. We report that CaCrg1 is important for virulence-related processes such as adhesion, hyphal elongation and membrane trafficking in response to this toxin. Using biochemical and genetic analysis we also found that CaCrg1 plays a role in complex sphingolipid pathway: it binds to exogenous short-chain ceramides in vitro, it interacts genetically with genes of glucosylceramide pathway and the deletion of CaCRG1 leads to significant changes in the abundance of phytoceramides. Finally we found that this novel lipid-related smMTase is required for virulence in the waxmoth Galleria mellonella, a model of infection.
- Subjects :
- Saccharomyces cerevisiae Proteins
Methyltransferase
Molecular Sequence Data
Saccharomyces cerevisiae
Cellular homeostasis
Virulence
Moths
Ceramides
Biochemistry
Article
Microbiology
Candida albicans
Animals
Amino Acid Sequence
Enzyme Inhibitors
Sequence Homology, Amino Acid
biology
Cell Membrane
Methyltransferases
General Medicine
biology.organism_classification
Sphingolipid
Recombinant Proteins
In vitro
Corpus albicans
Cantharidin
Molecular Medicine
Sequence Alignment
Gene Deletion
Subjects
Details
- ISSN :
- 15548937 and 15548929
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- ACS Chemical Biology
- Accession number :
- edsair.doi.dedup.....c7af39c7292ce58ca0087f3d0ef3b70e