Article

Acta Biochim Biophys Sin 2005,37:463-472

doi:10.1111/j.1745-7270.2005.00063.x

cDNA Array Analysis of the Differential Expression Change in Virulence-related Genes During the Development of Resistance in Candida albicans

Zheng XU1#, Yong-Bing CAO1#, Jun-Dong ZHANG1, Ying-Ying CAO1, Ping-Hui GAO1, De-Jun WANG1, Xu-Ping FU2, Kang YING2, Wan-Sheng CHEN1, and Yuan-Ying JIANG1*

1 Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai 200433, China;

2 State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, China

Abstract 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.

Key words Candida albicans; cDNA array; resistance; virulence

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