Both mouse models of systemic C. albicans infection have been used to evaluate novel diagnostics before a clinical trial (Nichterlein et al., 2003; Uno et al., 2007). Evaluation of new diagnostics in a host where systemic infection can be reliably induced demonstrated that serological tests for Candida mannan and β-glucan were more sensitive than nested PCR and blood culture for the prediction of systemic infection
in the mouse (Uno CHIR-99021 cell line et al., 2007). These tests have been further developed for clinical use, for example Platelia®Candida mannan antigen sandwich enzyme-linked immunosorbent assay (Bio-rad Laboratories) and Fungitell® assay (Associates of Cape Cod Inc.). Mouse models of systemic C. albicans infection have also played a critical role in the CP-868596 nmr early stages of antifungal drug development (Herrera & Guentzel,
1982; Andes, 2005), allowing in vivo antifungal efficacy to be determined. It is important, however, to consider that the results obtained for antifungal agents may differ in mice and humans. An example of this can be seen when triazole therapy is considered. In mice, triazoles are metabolized more quickly than in humans, due to differences in liver cytochrome P450 enzyme activity (Sugar & Liu, 2000). Inhibition of this activity in mice increased azole levels and improved infection outcome (Sugar & Liu, 2000; MacCallum & Odds, 2002b), although this was mouse strain dependent (MacCallum & Odds, 2002a). Potential antifungal antibodies
and vaccines have also been evaluated in mouse models of systemic C. albicans infection (Matthews et al., 2003; Spellberg et al., 2006; Cabezas et al., 2010). Mycograb, a human recombinant antibody against fungal HSP90, possessed antifungal activity in the mouse model and showed synergy when used in combination with amphotericin B (Matthews et al., 2003). Mycograb has since become the first anti-Candida antibody selleck to reach the clinic (Cabezas et al., 2010). The search for vaccines to prevent life-threatening systemic Candida infection in at-risk patients has also utilized the mouse infection model to evaluate whether vaccines are able to protect hosts from subsequent infection. In one example, a vaccine based on the administration of the N-terminus of C. albicans Als1p or Als3p was found to protect immunocompromised and immunocompetent mice from systemic candidiasis (Spellberg et al., 2006). This vaccine, NDV-3, is now being taken forward by NovaDigm and will enter Phase I clinical trials in 2011. Despite limitations due to differences between mice and humans, mouse models of systemic Candida infection have contributed considerably to our current appreciation of host–fungus interactions during systemic infection and have been essential tools in the development of new antifungal therapies and diagnostics.