Abstract
The conserved cAMP-dependent protein kinase (PKA) is composed of the regulatory and catalytic subunits and acts as the central component of the cAMP signaling pathway. In the human fungal pathogen Candida albicans, the PKA regulatory subunit Bcy1 plays a critical role in the regulation of cell differentiation and death. It has long been considered that Bcy1 is essential for cell viability in C. albicans. In the current study, surprisingly, we found that Bcy1 is not required for cell growth, and we successfully generated a bcy1/bcy1 null mutant in C. albicans. Deletion of BCY1 leads to multiple cellular morphologies and promotes the development of filaments. Filamentous and smooth colonies are two typical morphological types of the bcy1/bcy1 mutant, which can undergo spontaneous switching between the two types. Cells of filamentous colonies grow better on a number of different culture media and have a higher survival rate than cells of smooth colonies. In addition, deletion of BCY1 significantly increased the frequency of white-to-opaque switching on N-acetylglucosamine (GlcNAc)-containing medium. The bcy1/bcy1 null mutant generated herein provides the field a new resource to study the biological functions of the cAMP signaling pathway in C. albicans.
Highlights
The cAMP signaling pathway regulates a plethora of biological processes in eukaryotic organisms (Wang and Heitman, 1999; Pan et al, 2000; Gancedo, 2001; Chin et al, 2002; Chiaradonna et al, 2008)
The cAMP/protein kinase (PKA) pathway plays a critical role in the regulation of a number of features of the human fungal pathogen C. albicans (Hogan and Sundstrom, 2009; Huang, 2012)
We demonstrate that the two alleles of BCY1 could be deleted in C. albicans
Summary
The cAMP signaling pathway regulates a plethora of biological processes in eukaryotic organisms (Wang and Heitman, 1999; Pan et al, 2000; Gancedo, 2001; Chin et al, 2002; Chiaradonna et al, 2008). In the human fungal pathogen Candida albicans, this pathway plays a central role in the regulation of morphological transitions, carbon source utilization, quorum sensing, cell death, and virulence (Leberer et al, 2001; Rocha et al, 2001; Phillips et al, 2006; Biswas et al, 2007; Huang et al, 2010; Huang, 2012; Du et al, 2015). Bcy Regulates Phenotypic Transitions in C. albicans in a number of morphological forms, such as the yeast form, filaments (hyphae and pseudohyphae), and white, gray, and opaque cell types (Biswas et al, 2007; Whiteway and Bachewich, 2007; Huang, 2012). The alterations of cAMP levels modulate the activity of the cAMP-dependent protein kinase (PKA)
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