Conserved and Divergent Functions of the cAMP/PKA Signaling Pathway in Candida albicans and Candida tropicalis

Abstract

Fungal species undergo many morphological transitions to adapt to changing environments, an important quality especially in fungal pathogens. For decades, Candida albicans has been one of the most prevalent human fungal pathogens, and recently, the prevalence of Candida tropicalis as a causative agent of candidiasis has increased. In C. albicans, the ability to switch between yeast and hyphal forms is thought to be a key virulence factor and is regulated by multiple signaling cascades—including the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA), calcineurin, high-osmolarity glycerol (HOG), and mitogen-activated protein kinases (MAPK) signaling pathways—upon receiving environmental cues. The cAMP/PKA signaling pathway also triggers white-opaque switching in C. albicans. However, studies on C. tropicalis morphogenesis are limited. In this minireview, we discuss the regulation of the yeast-hypha transition, virulence, and white-opaque switching through the cAMP/PKA pathway in the closely related species C. albicans and C. tropicalis.

Keywords: C. tropicalis; Candida albicans; cAMP; hyphal growth; protein kinase A; white-opaque switching.

Figure 1

Regulatory models of the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway in C. albicans and C. tropicalis. Environmental cues activate cAMP/PKA in C. albicans (A) and C. tropicalis (B). Upon directly sensing environmental cues or being activated by Ras1, Cyr1 converts ATP to cAMP to bind the regulatory subunits of PKA (Bcy1) and liberate the catalytic subunits (Tpk1 and Tpk2). CaTpk1 is required for responding to stress (e.g., oxidative, osmotic, and thermal stressors), while CtTpk1 controls cell wall integrity and drug tolerance. In C. albicans, Tpk1 contributes to hyphal growth on solid media and Tpk2 is involved in hyphal growth in liquid media. In contrast, only Tpk2 contributes to hyphal growth on solid or in liquid media in C. tropicalis. In both species, Tpk1 and Tpk2 have redundant roles in vegetative growth. Furthermore, CtTpk1 and CtTpk2 share redundant functions in white-opaque switching and virulence, but in C. albicans, these two phenotypes are only controlled by Tpk2. GlcNAc induces both hyphal growth and white-opaque switching in C. albicans. In contrast, GlcNAc inhibits hyphal growth but promotes white-opaque switching in C. tropicalis. CO₂ induces white-opaque switching in C. albicans, but inhibits the same transition in C. tropicalis. Environmental pH regulates hyphal growth via Cyr1 in C. albicans. In contrast, environmental pH controls white-opaque switching through Ras1-cAMP/PKA in C. tropicalis. Red lines and arrows indicate differences and dash lines represent these interactions have not been characterized between C. albicans and C. tropicalis.