cDNA array analysis of the differential expression change in virulence-related genes during the development of resistance in Candida albicans.
Candida albicans is the most frequently isolated fungus in immunocompromised patients associated with mucosal and deep-tissue infections. To investigate the correlation between virulence and resistance on a gene expression profile in C. albicans, we examined the changes in virulence-related genes during the development of resistance in C. albicans from bone marrow transplant patients using a constructed cDNA array representing 3096 unigenes. In addition to the genes known to be associated with azole resistance, 16 virulence-related genes were identified, whose differential expressions were newly found to be associated with the resistant phenotype. Differential expressions for these genes were confirmed by RT-PCR independently. Furthermore, the up-regulation of EFG1, CPH2, TEC1, CDC24, SAP10, ALS9, SNF1, SPO72 and BDF1, and the down-regulation of RAD32, IPF3636 and UBI4 resulted in stronger virulence and invasiveness in the resistant isolates compared with susceptible ones. These findings provide a link between the expression of virulence genes and development of resistance during C. albicans infection in bone marrow transplant (BMT) patients, where C. albicans induces hyphal formation and expression change in multiple virulence factors.
Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Zheng
Z
Xu
Yong-Bing
YB
Cao
Jun-Dong
JD
Zhang
Ying-Ying
YY
Cao
Ping-Hui
PH
Gao
De-Jun
DJ
Wang
Xu-Ping
XP
Fu
Kang
K
Ying
Wan-Sheng
WS
Chen
Yuan-Ying
YY
Jiang
D002176:Candida albicans / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity*; D025141:Drug Resistance, Fungal / Q000235:genetics*; D015725:Fluconazole / Q000494:pharmacology; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics*
D015725:Fluconazole