Stage Specific Virulence Gene Activation by Host Signals

After the reliability of the reporter system had been confirmed in vitro, we used the reporter strain containing the SAP2P-FLP fusion in various experimental models of candidiasis to analyze the expression of the SAP2 gene at different stages of the infection process. In a model of oesophageal infection in mice in which C. albicans invades into the epithelium but does not disseminate hematogeneously into deep organs, significant SAP2 expression was not detected at any time point, indicating that activation of the SAP2 gene was not necessary for infection of the oesophageal epithelium. In contrast, in two mouse models of disseminated candidiasis in which the animals were infected either intraperitoneally or intravenously, a strong induction of the SAP gene occurred at late stages of systemic infection, after spread of the fungus into deep organs, but not before dissemination (Fig 3). These results suggest that the Sap2 proteinase has some function after the establishment of C. albicans in deep tissue, in which it is specifically activated by host signals, but that other proteinases might be needed during epithelial infection and invasion.

% MPAS cells

% MPAS cells

Figure 3. Expression of the SAP2 gene at various stages after intraperitoneal infection of mice.
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