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Protective role of trehalose during severe oxidative stress caused by hydrogen peroxide and the adaptive oxidative stress response in Candida albicans

Area de Microbiologia, Facultad de Biologia, Universidad de Murcia, Campus de Espinardo, E-30071 Murcia, Spain¹
Instituto de Investigaciones Biomédicas del CSIC, Unidad de Bioquimica y Genética de Levaduras, 28029 Madrid, Spain²

Author for correspondence: Juan-Carlos Argüelles. Tel: +34 968 36 71 31. Fax: +34 968 36 39 63. e-mail: arguelle{at}um.es

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.

Keywords: TPS1, cell protector, oxidative stress, adaptive response, opportunistic yeast pathogen

Abbreviations: ROS, reactive oxygen species; T-6P synthase, trehalose-6-phosphate synthase

^a Present address: Albert Einstein College of Medicine, Microbiology and Immunology. Golding Building, room 701, 1300 Morris Park Avenue, Bronx, NY 10461, USA

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