Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis.
To identify Candida albicans genes whose proteins are necessary for host cell interactions and virulence, a collection of C. albicans insertion mutants was screened for strains with reduced capacity to damage endothelial cells in vitro. This screen identified CKA2. CKA2 and its homologue CKA1 encode the catalytic subunits of the protein kinase CK2. cka2delta/cka2delta strains of C. albicans were constructed and found to have significantly reduced capacity to damage both endothelial cells and an oral epithelial cell line in vitro. Although these strains invaded endothelial cells similarly to the wild-type strain, they were defective in oral epithelial cell invasion. They were also hypersusceptible to hydrogen peroxide, but not to high salt or to cell wall damaging agents. A cka1delta/cka1delta mutant caused normal damage to both endothelial cells and oral epithelial cells, and it was not hypersusceptible to hydrogen peroxide. However, overexpression of CKA1 in a cka2delta/cka2delta strain restored wild-type phenotype. Although the cka2delta/cka2delta mutant had normal virulence in the mouse model of haematogenously disseminated candidiasis, it had significantly attenuated virulence in the mouse model of oropharyngeal candidiasis. Therefore, Cka2p governs the interactions of C. albicans with endothelial and oral epithelial cells in vitro and virulence during oropharyngeal candidiasis.
Chiang
Lisa Y
LY
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Sheppard
Donald C
DC
Bruno
Vincent M
VM
Mitchell
Aaron P
AP
Edwards
John E
JE
Filler
Scott G
SG
D000818:Animals; D002176:Candida albicans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D002177:Candidiasis / Q000382:microbiology*; D002180:Candidiasis, Oral / Q000382:microbiology*; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000382:microbiology; D004847:Epithelial Cells / Q000382:microbiology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009061:Mouth Mucosa / Q000382:microbiology; D016254:Mutagenesis, Insertional; D009960:Oropharynx / Q000166:cytology / Q000382:microbiology*; D018384:Oxidative Stress; D013047:Specific Pathogen-Free Organisms; D014774:Virulence
D005656:Fungal Proteins; D047390:Casein Kinase II