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Identification of Candida albicans genes induced during thrush offers insight into pathogenesis
Author(s) -
Cheng Shaoji,
Clancy Cornelius J.,
Checkley Mary Ann,
Handfield Martin,
Hillman Jeffrey D.,
ProgulskeFox Ann,
Lewin Alfred S.,
Fidel Paul L.,
Nguyen M. Hong
Publication year - 2003
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.2003.03521.x
Subject(s) - biology , candida albicans , corpus albicans , virulence , microbiology and biotechnology , gene , pathogenesis , thrush , bacterial adhesin , virulence factor , systemic candidiasis , genetics , immunology , cervical cancer , cancer , human papilloma virus
Summary 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.