The cellular response to the oxidative stress caused by hydrogen peroxide and its putative correlation with the stress protector trehalose was investigated in Candida albicans CAI.4 and the tps1/tps1 double mutant, which is deficient in trehalose synthesis. When exponential wild-type blastoconidia were exposed to high concentrations of hydrogen peroxide, they displayed a high cell survival, accompanied by a marked rise of intracellular trehalose. The latter is due to a moderate activation of trehalose synthase and the concomitant inactivation of neutral trehalase. Identical challenge in the tps1/tps1 double mutant severely reduced cell viability, a phenotype which was suppressed by overexpression of the TPS1 gene. Pretreatment of growing cultures from both strains with either a low, non-lethal concentration of H2O2 (0·5 mM) or a preincubation at 37 °C, induced an adaptive response that protected cells from being killed by a subsequent exposure to oxidative stress. During these mild oxidative preincubations, trehalose was not induced in CAI.4 cells and remained undetectable in their tps1/tps1 counterpart. Blastoconidia from the two strains exhibited a similar degree of cell protection during the adaptive response. The induction of trehalose accumulation by H2O2 was not due to an increased expression of TPS1 mRNA. These results are consistent with a mainly protective role of trehalose in C. albicans during direct oxidative stress but not during acquired oxidative tolerance.

In Candida albicans, trehalose plays an essential role as a protector of cell integrity against oxidative challenge. A double homozygous mutant, tps1/tps1, deficient in trehalose synthesis, displayed severe cell mortality when exposed to high H₂O₂ concentrations, compared with its congenic parental (CAI‐4) strain (Alvarez‐Peral et al., 2002). We have examined the putative role of a set of well‐known antioxidant enzymes as components of the defence mechanism against oxidative challenges. When exposed to mild non‐lethal oxidative treatment (0.5 mM H₂O₂), a significant induction of catalase, glutathione reductase (GR), and Cu,Zn‐superoxide dismutase (SOD) was recorded in tps1/tps1 exponential cultures. However, in CAI‐4 cells, subjected to the same conditions, there was only a clear activation of catalase, Mn‐SOD and Cu,Zn‐SOD activities. The degree of activation was always much more pronounced in the trehalose‐deficient mutant than in its wild‐type counterpart, except for Mn‐SOD activity. After exposure to severe oxidative stress (50 mM H₂O₂) only GR and catalase activities increased in tps1/tps1 cultures, whereas in CAI‐4 cells GR but not catalase was induced. In both cell strains, 50 mM H₂O₂ caused inhibition of the Mn‐ and Cu,Zn‐SOD isozymes, this inhibition being more pronounced in tps1/tps1 cells. C. albicans is able to acquire adaptive oxidative tolerance by pretreatment with a low non‐stressing concentration of H₂O₂ before exposure to a drastic oxidative challenge. When these antioxidant activities were measured during the adaptive response, a greater degree of enzymatic antioxidant induction was consistently observed in the tps1/tps1 mutant with respect to the CAI‐4 strain. Together with a higher intrinsic sensitivity of tps1/tps1 cells, we suggest that this unexpected increase might be explained in terms of a compensatory mechanism to overcome the lack of endogenous trehalose upon drastic oxidative exposure, although this induction was not sufficient to improve the percentage of cell viability. Copyright © 2003 John Wiley & Sons, Ltd.

In the pathogenic yeast Candida albicans, the MAP-kinase Hog1 mediates an essential protective role against oxidative stress, a feature shared with th