FIG 9.

Proposed pathobiological functions and regulatory mechanisms of the cAMP/PKA pathway in C. auris. A single adenylyl cyclase, Cyr1, catalyzes the conversion of ATP to cAMP. The cAMP binds to and releases the regulatory subunit of PKA, namely, Bcy1, from its two PKA catalytic subunits, Tpk1 and Tpk2. These have major and minor roles in pathogenicity, respectively. The activated PKA is involved in (i) cell growth at various temperatures, (ii) response and adaptation to stress, (iii) resistance to antifungal drugs, and (iii) the morphological transition of single cells to pseudohyphae. In addition, PKA can contribute to cell growth, response and adaptation to stress, and morphological transition in a Cyr1-independent manner. In particular, PKA plays unique roles in the transition of cells from haploid to diploid, in chitin and chitosan biosynthesis, and in biofilm formation in a Cyr1-independent manner. Most notably, Bcy1 and Tpk2, but not Cyr1 and Tpk1, have positive and negative roles, respectively, in the virulence of C. auris.