Abstract

As opportunistic pathogen, Candida albicans adapts to different environmental conditions and its corresponding stress. The Hog1 MAPK (Mitogen Activated Protein Kinase) was identified as the main MAPK involved in the response to osmotic stress. It was later shown that this MAPK is also involved in the response to a variety of stresses and therefore, its role in virulence, survival to phagocytes and establishment as commensal in the mouse gastrointestinal tract was reported. In this work, the role of Hog1 in osmotic stress is further analyzed, showing that this MAPK is involved in lipid homeostasis. The hog1 mutant accumulates lipid droplets when exposed to osmotic stress, leading to an increase in cell permeability and delaying the endocytic trafficking routes. Cek1, a MAPK also implicated in the response to osmotic challenge, did not play a role in lipid homeostasis indicating that Hog1 is the main MAP kinase in this response. The alteration on lipid metabolism observed in hog1 mutants is proposed to contribute to the sensitivity to osmotic stress.

Highlights

  • Candida albicans is a human commensal able to cause a great variety of infections ranging from superficial to systemic [1]

  • Signal transduction pathways mediated by Mitogen Activated Protein Kinases (MAPK) are one of the main mechanisms by which eukaryotic cells respond to extracellular stimuli to adapt and survive [6,7,8]

  • Previous work in S. cerevisiae reported that HOG pathway was not crucial for cell viability in the first hours after exposure to hyperosmotic challenge, but it was for efficient recovery and subsequent proliferation under osmostress [35]

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Summary

Introduction

Candida albicans is a human commensal able to cause a great variety of infections ranging from superficial to systemic [1]. C. albicans is the major cause of fungemia in hospitals of developed countries [2,3], other Candida species are increasing currently the incidence [4,5] Both as a commensal and during invasion, C. albicans need to face different external conditions in order to survive. Signal transduction pathways mediated by Mitogen Activated Protein Kinases (MAPK) are one of the main mechanisms by which eukaryotic cells respond to extracellular stimuli to adapt and survive [6,7,8] These MAPK pathways consist on a module of three kinases (named MAP kinase kinase kinase or MAPKKK; MAP kinase kinase or MAPKK; and a MAP kinase or MAPK) that became activated by sequential phosphorylation in response to different signals through other kinases, two-component systems or heterotrimeric G proteins. The activated MAPK triggers an adaptive response regulating the transcription of target genes or modulating enzymatic activities

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