Candida glabrata environmental stress response involves Saccharomyces cerevisiae Msn2/4 orthologous transcription factors

Abstract

SummaryWe determined the genome-wide environmental stress response (ESR) expression profile of Candida glabrata, a human pathogen related to Saccharomyces cerevisiae. Despite different habitats, C. glabrata, S. cerevisiae, Schizosaccharomyces pombe and Candida albicans have a qualitatively similar ESR. We investigate the function of the C. glabrata syntenic orthologues to the ESR transcription factor Msn2. The C. glabrata orthologues CgMsn2 and CgMsn4 contain a motif previously referred to as HD1 (homology domain 1) also present in Msn2 orthologues from fungi closely related to S. cerevisiae. We show that regions including this motif confer stress-regulated intracellular localization when expressed in S. cerevisiae. Site-directed mutagenesis confirms that nuclear export of CgMsn2 in C. glabrata requires an intact HD1. Transcript profiles of CgMsn2/4 mutants and CgMsn2 overexpression strains show that they regulate a part of the CgESR. CgMsn2 complements a S. cerevisiae msn2 null mutant and in stressed C. glabrata cells, rapidly translocates from the cytosol to the nucleus. CgMsn2 is required for full resistance against severe osmotic stress and rapid and full induction of trehalose synthesis genes (TPS1, TPS2). Constitutive activation of CgMsn2 is detrimental for C. glabrata. These results establish an Msn2-regulated general stress response in C. glabrata.

The Facultative Intracellular Pathogen Candida glabrata Subverts Macrophage Cytokine Production and Phagolysosome Maturation

“…Accordingly, an inactivation of these detoxifying enzymes leads to severe loss in virulence and viability inside immune cells (59). The oxidative stress response of C. glabrata is controlled by the transcription factors Yap1, Skn7, Msn2, and Msn4 (30,60,61), which mediate resistance of C. glabrata to H 2 O 2 and other oxidants. Additionally, C. glabrata possesses a catalase (Cta1p) that is required to survive oxidative stress (although this is dispensable in a mouse model of systemic infection) (60,62).…”

“…Primers used for strain construction are listed in Table I. GFP-Actt was cut out from pTD125 (29) and cloned via EcoRI/SalI into pADHpCg (30). A PCR fragment of the endogenous TRP1 gene containing a 59 untranslated region and a fragment of the 39 untranslated region were amplified from ATCC2001 genomic DNA.…”

A transcription factor, MrMsn2, in the dimorphic fungus Metarhizium rileyi is essential for dimorphism transition, aggravated pigmentation, conidiation and microsclerotia formation

“…This was unlike in ▵MoMsn2 in M. oryzae , ▵Bbmsn2 in  B. bassiana or ▵Mrmsn2 in M. robertsii , which decreased conidia production (Liu et al., 2013; Zhang et al ., 2014). Msn2‐like proteins do not appear to be important in transcriptional regulation of the stress response in C. albicans and V. dahliae (Nicholls et al ., 2004; Tian et al ., 2017), but are important in the stress response in C. glabrata , and S. cerevisiae (Schmitt and Mcentee, 1996; Roetzer et al ., 2008). Our research found that ▵MrMsn2 mutants were defective in response to osmotic, cell wall perturbation and oxidative stress (Fig.…”

“…Research on the function of Msn‐like transcriptional factors in pathogenicity is widespread for entomopathogenic, human pathogenic and phytopathogenic fungi (Roetzer et al ., 2008; Liu et al ., 2013; Zhang et al ., 2014). In M. rileyi , our data indicated that ▵MrMsn2 mutants were significantly less pathogenic than WT by both topical infection and injection assays (Fig.…”

“…Similar results were reported for ▵MoMsn2 mutants of M. oryzae , ▵Bbmsn2 mutants of B. bassiana , and ▵Mrmsn2 mutants of M. robertsii in which gene deletions cause decreased virulence (Liu et al ., 2013; Zhang et al ., 2014). In contrast, in C. glabrata , Msn2 was found to have no effect on virulence (Roetzer et al ., 2008). One explanation for this is that ▵MrMsn2 mutants counter oxidative stress from hosts in vivo (Song et al ., 2016a,b) and were hypersensitive to stress.…”