Factors Regulating Morphogenesis in Coccidioides Immitis

The parasitic cycle of Coccidioides immitis is unique among the human systemic fungal pathogens. However, at the level of cell wall biosynthesis and modification C. immitis demonstrates features which are shared by other fungal pathogens. Three distinct events in the morphogenesis of parasitic cells, or spherules, of Coccidioides are examined in this study. These include the diametric growth phase of round cells (young spherules), spherule segmentation, and endosporulation. Three enzymatic products of developing spherules have been suggested to participate in regulation of these successive morphogenetic stages of C. immitis. Preliminary evidence is presented that a s-1,3-endoglucanase contributes to plasticization of the round cell wall, and consequently plays a role in diametric expansion of young spherules. Results of earlier studies of a 34 kDa proteinase are reviewed which suggest that this wall-associated enzyme may function in development of the segmentation wall. Data from recent studies of a 100 kDa chitinase are presented which suggest that this enzyme participates in endosporulation of the parasitic cells. Morphogenetic studies of Coccidioides may lead to the identification of regulatory factors which are common to other pathogenic fungi, and therby, to the characterization of molecular targets for development of future antifungal reagents.