Possible roles of wall hydrolases in the morphogenesis ofCoccidioides immitis

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Abstract
We have used the human respiratory pathogen, Coccidioides immitis, as an experimental model to explore possible interrelationships of wall-associated hydrolases, cell growth, and reproduction. Preliminary evidence has been presented that suggests that certain wall hydrolases (glucanase, chitinase) may play key roles in cell development in this systemic pathogen. Initial differentiation of the parasitic cells from cylindrical arthroconidia involves a period of isotropic growth and results in formation of a multinucleate spherule (approximately 60 μm diameter). An endo-1,3-β-glucanase that may participate in this diametric growth phase has been isolated. Two distinct chitinase genes (cts1, cts2) have been isolated from C. immitis and shown to be members of different classes of this wall hydrolase. The class I chitinase (CTS2) demonstrates homology to a reported endochitinase of Saccharomyces cerevisiae that has been shown to be essential for yeast daughter cell release. CTS2 may play a pivotal role in isotropic growth, as well as differentiation and release of endospores from maternal spherules. In the absence of specific gene disruption and transformation experiments, these data are still circumstantial evidence for the functions of wall hydrolases in C. immitis development. However, we suggest our results provide further support for the concept that wall hydrolases represent rational molecular targets for future development of novel antifungal agents. Key words: Coccidioides, cell wall, β-glucanase, chitinase, morphogenesis.