The purpose of this proposal is to gain insight into the pathophysiology of renal candidiasis. Specifically, we are interested in elucidating the factors which predispose the kidney to invasion by blood-borne Candida species, particularly Candida albicans. The project encompasses the following objectives: 1) to determine the site and mechanism of C. albicans localization in the kidney; 2) to define the mechanism by which this organism traverses from the capillary into the lumen of the renal tubule; and 3) to determne the involvement of disulfide reductase in germ-tube formation. By injecting viable organisms directly into the renal artery of a rabbit, we will define the initial sites of C. albicans localization within the kidney. A rabbit infection model will then determine whether initial localization sites are those from which infections arise in vivo. To uncouple C. albicans kidney localization from the complex environment of the host, an isolated rabbit kidney perfusion technique will be utilized to study specific cellular interactions involved in renal candidiasis. In particular we will investigate whether initial kidney localization of C. albicans is mediated by a specific adherence factor(s) associted with this organism. Related studies will assess the relative importance of endothelial endocytosis, germ-tube formation, as well as proteases and phospholipases, in renal tubule penetration.