Morphogenic and genetic differences between Candida albicans strains are associated with keratomycosis virulence.
OBJECTIVE
To correlate the morphogenic and molecular traits that affect fungal virulence in human corneas.


METHODS
C. albicans wild-type strains SC5314 and VE175 were compared using in vitro growth kinetics, filamentation assays, and microarray analysis. Corneal virulence was assessed ex vivo by inoculating C. albicans onto superficially scarified human corneas that were processed after 1 and 3 days to measure hyphal penetration. For comparison, DSY459, a C. albicans homozygous deletion mutant deficient in secreted aspartyl proteinases (SAP) 4, 5, and 6, was evaluated.


RESULTS
C. albicans strain SC5314 was highly filamentous in vitro and more invasive in human corneal explants while VE175 demonstrated limited filamentation and less corneal invasion. Among 6,655 C. albicans genes, 9.0% significantly (p<.05) differed by 2 fold or more between SC5314 and VE175. Genes involved in fungal filamentation that were upregulated in strain SC5314 compared to VE175 included SAP5, SAP6, and other hypha-associated genes. Compared to wild-type strains, DSY459 had intermediate filamentation and stromal penetration.


CONCLUSIONS
Fungal genes involved in filamentation likely contribute to virulence differences between wild-type strains of C. albicans. The corneal pathogenicity of C. albicans involves the morphogenic transformation of yeasts into hyphae.
Hua
Xia
X
Department of Ophthalmology, Baylor College of Medicine, Houston, TX, USA.
Yuan
Xiaoyong
X
Mitchell
Bradley M
BM
Lorenz
Michael C
MC
O'Day
Denis M
DM
Wilhelmus
Kirk R
KR
D002176:Candida albicans / Q000166:cytology / Q000235:genetics* / Q000472:pathogenicity*; D003315:Cornea / Q000382:microbiology / Q000473:pathology; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D016681:Genome, Fungal / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007634:Keratitis / Q000235:genetics / Q000382:microbiology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence
D005656:Fungal Proteins