Catalytic isoforms Tpk1 and Tpk2 of Candida albicans PKA have non‐redundant roles in stress response and glycogen storage

Abstract

Candida albicans cAMP-dependent protein kinase (PKA) is coded by two catalytic subunits (TPK1 and TPK2 ) and one regulatory subunit (BCY1 ). In this organism the cAMP/PKA signalling pathway mediates basic cellular processes, such as the yeastto-hyphae transition and cell cycle regulation. In the present study, we investigated the role of C. albicans PKA in response to saline, heat and oxidative stresses as well as in glycogen storage. To fine-tune the analysis, we performed the studies on several C. albicans PKA mutants having heterozygous or homozygous deletions of TPK1 and/or TPK2 in a different BCY1 genetic background. We observed that tpk1 /tpk1 strains developed a lower tolerance to saline exposure, heat shock and oxidative stress, while wild-type and tpk2 /tpk2 mutants were resistant to these stresses, indicating that both isoforms play different roles in the stress response pathway. We also found that regardless of the TPK background, heterozygous and homozygous BCY1 mutants were highly sensitive to heat treatment. Surprisingly, we observed that those strains devoid of one or both TPK1 alleles were defective in glycogen storage, while strains lacking Tpk2 accumulated higher levels of the polysaccharide, indicating that Tpk1 and Tpk2 have opposite roles in carbohydrate metabolism.

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…The cAMP-dependent PKA is composed of the two catalytic subunits Tpk1 and Tpk2, along with the regulatory subunit Bcy1, and is critical for the regulation of stress responses (204). tpk1 mutants have a lower tolerance to saline exposure, oxidative stress, and heat shock than do wild-type cells or tpk2 mutants (204).…”

Metabolism impacts upon Candida immunogenicity and pathogenicity at multiple levels

“…These effects, which are mediated partly through PKA signalling [41], may relate to the effects of metabolic adaptation upon the cellular abundances of osmolytes such as glycerol, and antioxidants such as glutathione and trehalose [34,42,43]. Glycerol and trehalose are synthesised via short metabolic branches off the glycolytic pathway.…”

Posttranslational Modifications of Proteins in the Pathobiology of Medically Relevant Fungi

“…Additionally, protein phosphorylation, a ubiquitous and reversible modification that is crucial for the regulation of multiple cellular events (153), regulates MAP kinase and two-component signaling cascades in fungal pathogens (80,186). Also, protein phosphorylation via cAMP-protein kinase A signaling contributes to fungal virulence through regulation of yeast-hypha morphogenesis and stress resistance in C. albicans (13,14,45) and mating, capsule formation, and melanin production in C. neoformans (2). Not surprisingly, protein phosphorylation has been studied extensively, and its role in yeast biology and fungal pathogenicity has been reviewed elsewhere (7,112,143).…”