Candida species cause approximately 11% of all bloodstream infections (reviewed in MacCallum, 2010), with C. albicans generally the most frequently isolated fungal species. It should be noted,

however, that in some geographical areas and in certain patient groups, other Candida species are more commonly isolated (reviewed in MacCallum, 2010). This frequent isolation of C. albicans is partly due to the fact that this species is the most common commensal, but may also be a reflection of the greater virulence of this species (Arendrup et al., 2002). In general, isolates obtained Olaparib from blood samples are identical, or highly similar, to those obtained from commensal sites of the same individuals, suggesting endogenous origins of infection (Bougnoux

et al., 2006; Odds et al., 2006; Miranda et al., 2009). One of the major problems with clinical systemic Candida infection is the difficulty in the diagnosis of infection. Bloodstream Candida infections tend to present clinically with nonspecific symptoms, similar to those seen with systemic bacterial infections. This can lead to delays in the initiation of effective antifungal therapy, as antifungals may HIF-1 pathway not be administered until the patient fails to respond to antibacterials. These delays contribute to the high mortality rates (>40%) associated with Candida bloodstream infection (Morrell et al., 2005), which can be further compounded by intrinsic or acquired antifungal IMP dehydrogenase drug resistance of Candida species (Sanglard & Odds, 2002; Ostrosky-Zeichner et al., 2003). Because of the problems in the diagnosis of human infection, models of systemic Candida infection are essential for our understanding of disease initiation and progression, and also to allow the development and evaluation of novel, more effective,

diagnostics and therapies. In recent years, minihosts (e.g. Drosophila melanogaster, Caenorhabditis elegans and Galleria mellonella larvae; reviewed in Chamilos et al., 2007) have been used to study aspects of Candida disseminated infection; however, it is only in mammalian hosts that fungal disease can be fully studied. Although larger mammals, such as piglets, rabbits, guinea-pigs and rats, can be used to investigate candidiasis, the majority of studies have been carried out in mice. This is mainly due to economic factors, ease of handling, the availability of knockout mouse strains and other reagents for analyses of host responses and the availability of well-characterized, reproducible infection models. This review discusses murine models of systemic Candida infection, their contribution to our understanding of these infections and their use to evaluate diagnostics and therapies. Murine models of disseminated Candida infection fall into two main categories: the intravenous infection model and the gastrointestinal colonization and dissemination model. This review focuses mainly on C.