Identification of Candida albicans genes induced during thrush offers insight into pathogenesis.
Candida albicans causes a wide spectrum of diseases, ranging from mucocutaneous infections like oral thrush to disseminated candidiasis. Screening for C. albicans genes expressed within infected hosts might advance understanding of candidal pathogenesis, but is impractical using existing techniques. In this study, we used an antibody-based strategy to identify C. albicans genes expressed during thrush. We adsorbed sera from HIV-infected patients with thrush against candidal cells grown in vitro and screened a C. albicans genomic expression library. We identified 10 genes encoding immunogenic antigens and used reverse transcription-polymerase chain reaction to verify that they were induced within thrush pseudomembranes recovered from a patient. The in vivo induced genes are involved in diverse functions, including regulation of yeast-hyphal morphogenesis, adhesion to host cells, nutrient uptake, phospholipid biosynthesis and amino acid catabolism. Four genes encode known virulence determinants (HWP1, CST20, CPP1 and RBF1). Another gene, LPD1, for which a role in candidal pathogenesis is unknown, encodes a protein homologous to a bacterial virulence determinant. Most importantly, disruption of CaNOT5, a newly identified gene, conferred defects in morphogenesis, decreased adherence to human buccal epithelial cells and attenuated mortality during murine disseminated candidiasis, proving that our strategy can identify genes encoding novel virulence determinants.
Cheng
Shaoji
S
Department of Medicine, University of Florida College of Medicine, Gainesville 32610, USA.
Clancy
Cornelius J
CJ
Checkley
Mary Ann
MA
Handfield
Martin
M
Hillman
Jeffrey D
JD
Progulske-Fox
Ann
A
Lewin
Alfred S
AS
Fidel
Paul L
PL
Nguyen
M Hong
MH
D017088:AIDS-Related Opportunistic Infections / Q000382:microbiology / Q000503:physiopathology; D000328:Adult; D000818:Animals; D000908:Antibodies, Fungal / Q000276:immunology; D000946:Antigens, Fungal / Q000235:genetics* / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D002180:Candidiasis, Oral / Q000382:microbiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D015658:HIV Infections / Q000150:complications; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics
D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D005656:Fungal Proteins