Protein kinase A and fungal virulence

Abstract

Diverse fungal species are the cause of devastating agricultural and human diseases. As successful pathogenesis is dependent upon the ability of the fungus to adapt to the nutritional and chemical environment of the host, the understanding of signaling pathways required for such adaptation will provide insights into the virulence of these pathogens and the potential identification of novel targets for antifungal intervention. The cAMP-PKA signaling pathway is well conserved across eukaryotes. In the nonpathogenic yeast, S. cerevisiae, PKA is activated in response to extracellular nutrients and subsequently regulates metabolism and growth. Importantly, this pathway is also a regulator of pathogenesis, as defects in PKA signaling lead to an attenuation of virulence in diverse plant and human pathogenic fungi. This review will compare and contrast PKA signaling in S. cerevisiae vs. various pathogenic species and provide a framework for the role of this pathway in regulating fungal virulence.

Cryptococcus neoformanscan form titan-like cellsin vitroin response to multiple signals that require the activation of several transduction pathways

“…We argue that a partial inhibition of the respiratory chain can trigger a stress signal that results in a stop of the cell cycle and allows cellular size increase. In this regard, it could be assumed that a limitation in the respiratory capacity might lead the organism to generate energy, at least in part, by fermentative metabolism, a situation that has been associated to increased PKA activity in many fungi [64]. Although C. neoformans is mainly a respiratory yeast, it has been shown that it can produce both ethanol and acetate in vitro and in vivo [65, 66], so a similar activation of the PKA activity could also occur in these conditions.…”

Developmental Growth Control Exerted via the Protein A Kinase Tpk2 in Ashbya gossypii

“…Key decisions on cell fate in fungi are gated to control metabolism, stress response, pathogenicity, growth, and developmental switches for entering quiescence, sporulation, or breaking the dormancy of spores (2,33,34). Signal transduction cascades play an essential role to parse environmental information and result in appropriate cellular responses (1).…”

“…Morphogenetic decisions often are accompanied with virulence. Accordingly, the PKA pathway was also identified as a key regulator of fungal pathogenicity (2). In Candida albicans Tpk2 regulates dimorphism, and tpk2 strains are crippled in their ability to invade tissues and thus reduced in virulence (44).…”

“…Transmembrane proteins act as sensors for external environmental stimuli and signal through conserved signal transduction pathways, including mitogen-activated protein kinase (MAPK) modules, the calcium/calcineurin pathway, and the cyclic AMP (cAMP) pathway, and have been studied in a large variety of fungi (1). Often, these pathways harbor genes required for fungal pathogenicity of plant or animal pathogens (2,3). Saccharomyces cerevisiae adapts to drastically changing environmental conditions by the activation of an environmental stress response (4).…”

Host‐induced gene silencing of an important pathogenicity factor PsCPK1 in Puccinia striiformis f. sp. tritici enhances resistance of wheat to stripe rust

“…From 6 to 8 days after infection, symptoms of chlorosis will be observed, whereas sporulation commences after approximately 12-14 days under favourable conditions. The cyclic adenosine monophosphate protein kinase A (cAMP-PKA) signalling pathway is well conserved across eukaryotes and has been proved to participate in virulence, morphogenesis and development in diverse fungi (Bahn and Sundstrom, 2001;Fuller and Rhodes, 2012). In Saccharomyces cerevisiae, cAMP-dependent protein kinase has a vital role in controlling proliferation, stress resistance, metabolism and the availability of nutrients (Thevelein and De Winde, 1999;Toda et al, 1987).…”