Taken together, these results indicate that DUR1,2 and the encoded urea amidolyase act as a virulence factor for murine disseminated candidiasis and potentially for other infections caused by C. albicans. From a more global perspective, they suggest an important role of urea availability in determining the location and severity of C. 3,4,5-Trimethoxyphenylacetic acid albicans infections. Notably, the organs in which C. albicans can establish persistent colonization are those with the highest urea contents. Urea in the kidney is concentrated along the renal corticomedullary axis by the function of several 
active urea transporters. In Folinic acid calcium salt pentahydrate healthy kidneys urea is further concentrated and sequestered in collecting ducts, but fungal infection, tissue necrosis, and the host inflammatory response may cause accumulation of urea, which further enhances virulence. In addition to providing nitrogen for growth, our data indicate that urea metabolism by C. albicans has profound effects on the host inflammatory and immune responses. In addition to its established role in escape from macrophages, urea metabolism has both local and systemic effects on the host immune response. The long blood circulating time and progressive phagocytic uptake of USPIO particles enabled us to use MRI imaging as a tool to non-invasively follow phagocyte recruitment and tissue inflammation in infected mice. These imaging results were validated by histopathology, immunohistochemistry and expression of inflammatory cytokines and the activated phagocytic marker iNOS. The 50-fold increase in iNOS mRNA expression in WT C. albicans infected kidneys could result from increased neutrophil or M1 macrophage infiltration. Increased survival of mice infected with the dur1,2 mutant may be explained in part by its inability to persist beyond 7 days PI in kidneys of infected mice. A number of previous pathogenesis studies indicated that kidney is the key battleground for survival of candidiasis. Approximately 90% of C. albicans cells are cleared from mouse blood within 3 min of tail vein injection. In addition to kidney, other organs including brain, liver, lung, and spleen are initially colonized by C. albicans in immunocompetent mice, but except for kidney and to a lesser degree brain, all the organs are cleared by 4 days PI. Colonization selectively persists in the kidney in both mice and humans. C. albicans infection is associated with increased levels of pro inflammatory monocyte derived cytokines such as TNFa, IL-1, and IL-6 as well as high IL-10, which contribute to the suppression of immunity against candidiasis. In addition, Th2 responses, indicated by high levels of IL-4, are detrimental to a host/patient with disseminated candidiasis. We recently reported that the decreased virulence of a C. albicans hmx1 mutant is associated with alterations in systemic cytokine levels that indicate a more balanced host immune response. We propose that the loss of urea degradation that results from deletion of DUR1,2 has a similar balancing effect on systemic host immunity. Urea metabolism by C. albicans in the kidney also exacerbates local host inflammatory gene responses. Several of these chemokines attract neutrophils, and their persistence causes collateral damage to host tissue that may lead to tissue necrosis and impaired kidney function. The improved kidney function and reduced Candida colonization and inflammatory reactions associated with KWN6 infection suggest that the role of urea metabolism in colonization and inflammation in the kidney involves the control of local inflammatory reactions, particularly neutrophils at early time points. For, example, MIP2 and IL-7 were up-regulated locally in WT infected kidneys compared with the KWN6 infected kidneys but were not altered systemically. This more balanced immune response may prevent the chronic stage of colonization of the renal medulla and pelvis.