Functional studies of GST2, a morphogenetic transition regulator on nitrogen starvation, in Candida albicans

Abstract

Candida albicans is a major human fungal pathogen, which undergoes morphological transition from the budding yeast form to filamentous growth in response to nitrogen starvation. In this study, C. albicans Gst2p, a new morphogenetic regulatory gene induced by nitrogen starvation was identified and characterized. C. albicans Gst2p displayed glutathione transferase (GST) activity and is required in response to peroxide. Surprisingly, the Δgst2 mutant displayed predominantly yeast phase growth on solid nitrogen limited media, whereas the wild-type strain formed pseudohyphae efficiently under the same conditions. Furthermore, Gst2p is strongly induced by nitrogen starvation. The morphological defect of Δgst2 mutant was not rescued by overexpression of Ras1p, Cph1p, or Efg1p, but was rescued by either overexpression of a hyperactive RAS1G13V allele or by exogenous addition of cyclic adenosine monophosphate (cAMP). The artificial expression was consistent with the Ras1-cAMP pathway as a possible downstream target of Gst2p. The deletion of GST2 also increased levels of MEP2 and MEP1 transcripts by elevating GLN3 expression under conditions of nitrogen starvation. These findings suggest that Gst2p may be one of the regulators of GLN3 transcription, the regulation of which controls ammonium permease expression, and a significant component of filamentation under conditions of nitrogen starvation in C. albicans.