Sorbic acid stress activates the Candida glabrata high osmolarity glycerol MAP kinase pathway

Abstract

Weak organic acids such as sorbic acid are important food preservatives and powerful fungistatic agents. These compounds accumulate in the cytosol and disturb the cellular pH and energy homeostasis. Candida glabrata is in many aspects similar to Saccharomyces cerevisiae. However, with regard to confrontation to sorbic acid, two of the principal response pathways behave differently in C. glabrata. In yeast, sorbic acid stress causes activation of many genes via the transcription factors Msn2 and Msn4. The C. glabrata homologs CgMsn2 and CgMsn4 are apparently not activated by sorbic acid. In contrast, in C. glabrata the high osmolarity glycerol (HOG) pathway is activated by sorbic acid. Here we show that the MAP kinase of the HOG pathway, CgHog1, becomes phosphorylated and has a function for weak acid stress resistance. Transcript profiling of weak acid treated C. glabrata cells suggests a broad and very similar response pattern of cells lacking CgHog1 compared to wild type which is over lapping with but distinct from S. cerevisiae. The PDR12 gene was the highest induced gene in both species and it required CgHog1 for full expression. Our results support flexibility of the response cues for general stress signaling pathways, even between closely related yeasts, and functional extension of a specific response pathway.

Competition ofCandida glabrataagainstLactobacillusis Hog1 dependent

“…Unlike in S. cerevisiae , C. glabrata Hog1 confers resistance not only to osmotic stress and sorbic acid stress but also to other stress types (Jandric et al, 2013, Srivastava et al, 2015, Gregori et al, 2007). To cover monocarboxylic acids, we chose lactic acid and PAA in addition to sorbic acid as model substrates.…”

“…A fully complementing GFP‐tagged CgHog1 (Jandric et al, 2013) was used for microscopy to determine the ratio of nuclear versus cytosolic fluorescence (N/C‐ratio) (Figure 3a). As reference for nuclear accumulation of CgHog1, 0.6 M of NaCl was used, which showed an N/C ratio of 1.9 ( p  < 0.0001), whereas the untreated control had an N/C ratio of 1.4.…”

“…In C. glabrata , deletion of main constituents of the HOG pathway, such as HOG1 , PBS2 , SSK2 , and SHO1 , has been previously shown to induce susceptibility against not only osmotic stress but also weak organic acids (i.e., acetate or sorbate), heat stress, oxidative stress, and high external iron levels. This indicates that this pathway is responsible for a variety of stress responses in C. glabrata (Gregori et al, 2007, Kaloriti et al, 2012, Jandric et al, 2013, Srivastava et al, 2015). …”

“…Unless indicated otherwise, Candida glabrata strain BG14 ( ura3 Δ( −285 + 932)::Tn903NeoR ) (Cormack & Falkow, 1999) was used as reference strain. The Cg hog1 Δ mutant and the pHog1‐GFP plasmid were created as described previously (Jandric et al, 2013). The Cg hog1 Δ mutant strain was confirmed by whole genome sequencing (30× coverage) to contain no additional mutations other than the intended knock out (data not shown).…”

“…In Schizosaccharomyces pombe , the orthologous Spc1 MAPK pathway is not only activated by osmotic stress but also by a wide range of environmental stresses such as UV radiation and heat stress (Toone et al, 1998, Chen et al, 2003). Furthermore, C. glabrata CgHog1 is activated by weak organic acid stress (Jandric et al, 2013, Gregori et al, 2007). In C. albicans , the transcriptional response to osmotic stress and heavy metal stress is partly Hog1 dependent (Enjalbert et al, 2006).…”