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Vol. 19, Issue 10, 4393-4403, October 2008

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MNL1 Regulates Weak Acid–induced Stress Responses of the Fungal Pathogen Candida albicans

Mark Ramsdale^*,, Laura Selway^*, David Stead^*, Jan Walker^*, Zhikang Yin^*, Susan M. Nicholls^*, Jonathan Crowe^*, Emma M. Sheils^*, and Alistair J.P. Brown^*

*Institute of Medical Sciences, School of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, United Kingdom; and School of Biosciences, University of Exeter, Exeter, Devon, EX4 4PS, United Kingdom

Submitted September 21, 2007; Revised June 30, 2008; Accepted July 11, 2008
Monitoring Editor: Mark J. Solomon

MNL1, the Candida albicans homologue of an orphan Msn2-like gene (YER130c in Saccharomyces cerevisiae) has no known function. Here we report that MNL1 regulates weak acid stress responses. Deletion of MNL1 prevents the long-term adaptation of C. albicans cells to weak acid stresses and compromises their global transcriptional response under these conditions. The promoters of Mnl1-dependent genes contain a novel STRE-like element (SLE) that imposes Mnl1-dependent, weak acid stress–induced transcription upon a lacZ reporter in C. albicans. The SLE (HHYYCCCCTTYTY) is related to the Nrg1 response element (NRE) element recognized by the transcriptional repressor Nrg1. Deletion of NRG1 partially restores the ability of C. albicans mnl1 cells to adapt to weak acid stress, indicating that Mnl1 and Nrg1 act antagonistically to regulate this response. Molecular, microarray, and proteomic analyses revealed that Mnl1-dependent adaptation does not occur in cells exposed to proapoptotic or pronecrotic doses of weak acid, suggesting that Ras-pathway activation might suppress the Mnl1-dependent weak acid response in dying cells. Our work defines a role for this YER130c orthologue in stress adaptation and cell death.

Address correspondence to: Mark Ramsdale (m.ramsdale{at}exeter.ac.uk)

Abbreviations used: NRE, Nrg1 response element; SLE, STRE-like element.

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