Differential activation of a Candida albicans virulence gene family duringinfection

The yeast Candida albicans is a harmless commensal in most healthy people, but it causes superficial as well as life-threatening systemic infections i n immunocompromised patients. C. albicans can colonize or infect virtually all body sites because of its high adaptability to different host niches, w hich involves the activation of appropriate sets of genes in response to co mplex environmental signals. we have used an in vivo expression technology that is based on genetic recombination as a reporter of gene expression to monitor the differential activation of individual members of a gene family encoding secreted aspartic proteinases (Saps), which have been implicated i n C. albicans virulence, at various stages of the infection process. Our re sults demonstrate that SAP expression depends on the type of infection, wit h different SAP isogenes being activated during systemic disease as compare d with mucosal infection. In addition, the activation of individual SAP gen es depends on the progress of the infection, some members of the gene famil y being induced immediately after contact with the host, whereas others are expressed only after dissemination into deep organs. In the latter case, t he number of invading organisms determines whether induction of a virulence gene is necessary for successful infection. The in vivo expression technol ogy allows the elucidation of gene expression patterns at different stages of the fungus-host interaction, thereby revealing regulatory adaptation mec hanisms that make C, albicans the most successful fungal pathogen of humans and, at the same time, identifying the stage of an infection at which cert ain virulence genes may play a role.