The authors thank E. Veal for intellectual input. This work was funded by the UK Biotechnology and Biological Research Council [J.Q. BB/K016393/1; A.J.P.B. BB/K017365/1], the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [D.M.M. NC/N002482/1] and the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology [097377]). D.M.M. and A.J.P.B. are also supported by the MRC Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1).Peer reviewedPublisher PD

Brown, Alistair J P

Day, Alison M

Herrero-de-Dios, Carmen M.

MacCallum, Donna M

Quinn, Janet

Scientific Reports

English

AbstractStress-activated protein kinase (SAPK) pathways are evolutionarily conserved eukaryotic signalling modules that are essential for the virulence of human pathogenic fungi. The Hog1 SAPK in Candida albicans is robustly phosphorylated in response to a number of host-imposed stresses, and is essential for virulence. The current dogma is that stress-induced phosphorylation activates the SAPK, and promotes its nuclear accumulation that is necessary for the expression of SAPK-dependent stress-protective genes. Here we challenge this dogma. C. albicans strains were constructed in which Hog1 was either tethered to the plasma membrane or constitutively nuclear. Strikingly, tethering Hog1 to the plasma membrane did not abrogate stress resistance or stress-induced gene expression. Furthermore, preventing the nuclear accumulation of Hog1 had no impact on C. albicans virulence in two distinct models of systemic infection. However, tethering Hog1 to the plasma membrane did impact on signal fidelity, and on the magnitude and kinetics of the stress-induced phosphorylation of this SAPK. Taken together, these findings challenge the dogma that nuclear accumulation of SAPKs is a pre-requisite for SAPK-dependent gene expression, and reveal that stress-induced nuclear accumulation of Hog1 is dispensable for the virulence of a major human fungal pathogen.</jats:p

Alison M. Day

Carmen M. Herrero-de-Dios

Donna M. MacCallum

Alistair J. P. Brown

Janet Quinn

Crossref

Stress-induced nuclear accumulation is dispensable for Hog1-dependent gene expression and virulence in a fungal pathogen

The authors thank E. Veal for intellectual input. This work was funded by the UK Biotechnology and Biological Research Council [J.Q. BB/K016393/1; A.J.P.B. BB/K017365/1], the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) [D.M.M. NC/N002482/1] and the Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology [097377]). D.M.M. and A.J.P.B. are also supported by the MRC Centre for Medical Mycology at the University of Aberdeen (MR/N006364/1).Peer reviewe

The Open University

http://link.springer.com/article/10.1038/s41598-017-14756-4

Stress-induced nuclear accumulation is dispensable for Hog1-dependent gene expression and virulence in a fungal pathogen

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The Open University