Abstract
The cell wall integrity pathway (CWI) plays an important role in the biogenesis of the cell wall in Candida albicans and other fungi. In the present work, the C. albicans MKK2 gene that encodes the putative MAPKK of this pathway was deleted in different backgrounds and the phenotypes of the resultant mutants were characterised. We show here that Mkk2 mediates the phosphorylation of the Mkc1 MAPK in response to cell wall assembly interfering agents such as zymolyase or tunicamycin and also to oxidative stress. Remarkably, mkk2 and mkc1 mutants display related but distinguishable- cell wall associated phenotypes and differ in the pattern of MAPK phosphorylation under different stress conditions. mkk2 and mkc1 mutants display an altered expression of GSC1, CEK1 and CRH11 genes at different temperatures. Combined deletion of MKK2 with HST7 supports a cooperative role for the Cek1-mediated and CWI pathways in regulating cell wall architecture under vegetative growth. However, and in contrast to Mkc1, Mkk2 does not seem to play a role in the virulence of C. albicans in the mouse systemic model or the Galleria mellonella model of infection.
Highlights
Maintenance of fungal integrity relies on proper signalling mechanisms within the cell
Unlike S. cerevisiae that has two MAPKK proteins in the cell wall integrity pathway (CWI) pathway, ScMkk1 and ScMkk2, only one gene named MKK2 is present in C. albicans
The precise point where the signal generated by ROS feeds into the CWI MAPK pathway is not known, this work indicates that it occurs upstream Mkk2
Summary
Maintenance of fungal integrity relies on proper signalling mechanisms within the cell. Harmful environmental conditions trigger signalling pathways that lead to appropriate transcriptional responses While these responses are important to every living organism, they are crucial in pathogens, where continuous challenge to host defences may lead to efficient eradication of the pathogen or lead to the development of disease. Candida albicans is an opportunistic pathogen that inhabits the gastrointestinal and vaginal tract of humans, being able to cause different diseases upon alteration of host defences. Within these niches, C. albicans may be exposed to changes in pH, oxidative stress, detergents or interactions with other components of the host microbiota and host immune defences that trigger in the fungus a coordinated response. The Cek MAPK was isolated as a dominant negative gene that interfered with pheromone-mediated cell cycle arrest
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