A Conserved Stress-activated Protein Kinase Regulates a Core Stress Response in the Human PathogenCandida albicans

Abstract

Previous work has implicated the Hog1 stress-activated protein kinase (SAPK) in osmotic and oxidative stress responses in the human pathogen Candida albicans. In this study, we have characterized the role of Hog1 in mediating these and other stress responses in C. albicans. We provide evidence that a SAPK-dependent core stress response exists in this pathogen. The Hog1 SAPK is phosphorylated and it accumulates in the nucleus in response to diverse stress conditions. In addition, we have identified Hog1-regulated genes that are induced in response to stress conditions that activate Hog1. These analyses reveal both activator and repressor functions for the Hog1 SAPK. Our results also demonstrate that stress cross-protection, a classical hallmark of the core stress response, occurs in C. albicans between stresses that activate the Hog1 SAPK. Importantly, we find that the core stress response in C. albicans has adapted to the environmental niche of this human pathogen. This niche specificity is reflected by the specific environmental conditions that drive the Hog1-regulated core stress response in C. albicans and by differences in the molecular circuitry that control this response.

Fungal Morphogenesis

“…The high osmolarity glycerol (HOG) mitogen-associated protein kinase pathway plays a central role in stress responses in C. albicans (Alonso-Monge et al 1999;Smith et al 2004;Arana et al 2005;Enjalbert et al 2006). Hog1 is activated by osmotic, oxidative, and heavy metal stress.…”

Transcript Profiles of Candida albicans Cortical Actin Patch Mutants Reflect Their Cellular Defects: Contribution of the Hog1p and Mkc1p Signaling Pathways

“…Activation of either the Sho1p-Ste11p or the Sln1p-Ssk1p branch or both leads to phosphorylation and activation of scaffold protein kinase Pbs2p, followed by phosphorylation, activation, and nuclear translocation of Hog1p (43). C. albicans Hog1p is similarly phosphorylated and translocated to the nucleus as part of the response (50). The long-term adaptation to hyperosmotic stress involves a change in transcriptional expression mediated by Hog1p phosphorylation of several transcription factors, including Sko1p, Hot1p, and Smp1p (2,3,12,44).…”

The Same Receptor, G Protein, and Mitogen-activated Protein Kinase Pathway Activate Different Downstream Regulators in the Alternative White and Opaque Pheromone Responses ofCandida albicans

“…The pathogenic yeast Candida albicans also uses MAP kinase pathways in the mating process (Chen et al, 2002;Magee et al, 2002), filamentation (Liu et al, 1994;Csank et al, 1998;Navarro-Garcia et al, 1998), and osmoregulation (Alonso-Monge et al, 1999;Smith et al, 2004). But C. albicans has one additional and unique response to mating pheromones that so far has not been identified in other yeast .…”

“…These alternative signals are then transduced through the same heterotrimeric G protein to activate the same MAP kinase pathway, which in turn activates the same downstream regulators that elicit similar mating responses, including G1 arrest, polarization, and shmooing (Sprague et al, 1983;Bender and Sprague, 1986;Leberer et al, 1997). Other fungi, including Magnaporthe grisea (Dixon et al, 1999;Zhao et al, 2005b) Neurospora crassa (Li et al, 2005), and Cryptococcus neoformans (Davidson et al, 2003;Kraus et al, 2003;Bahn et al, 2005) also use MAP kinase pathways for a variety of responses (Kruppa and Calderone, 2006).The pathogenic yeast Candida albicans also uses MAP kinase pathways in the mating process (Chen et al, 2002;Magee et al, 2002), filamentation (Liu et al, 1994;Csank et al, 1998;Navarro-Garcia et al, 1998), and osmoregulation (Alonso-Monge et al, 1999;Smith et al, 2004). But C. albicans has one additional and unique response to mating pheromones that so far has not been identified in other yeast .…”