Yeast
responses to stress induced by the herbicide 2,4-D: role of Pdr1p/Pdr3p- and
Msn2p/Msn4p-regulated genes.
Miguel Cacho Teixeira, Tânia Simões, Pedro Miguel Santos, Alexandra R. Fernandes,
Isabel Sá-Correia
CEBQ/Biological Sciences, Instituto Superior Técnico, Av. Rovisco Pais, Lisboa,
1049-001, Portugal (mnpct@ist.utl.pt)
The intensive use of herbicides may give rise to a number of toxicological problems and has led to the emergence of resistant weeds. We have been using Saccharomyces cerevisiae as an eukaryotic experimental model to identify determinants and mechanisms of adaptation and resistance to 2,4-dichlorophenoxyacetic acid (2,4-D). Following the demonstration that Pdr1/Pdr3 and Msn2/Msn4 transcription regulators are required for adaptation to 2,4-D, the participation of their target genes in this phenomenon was examined. Adaptation involves the Pdr1/Pdr3-dependent rapid and transient transcriptional activation of PDR5 and TPO1, encoding putative ABC and MFS multidrug transporters, respectively. Msn2/Msn4-regulated genes involved in protein folding, defense against ROS and energy metabolism were also implicated in this stress response, by proteomic and gene-by-gene approaches. Moreover, adaptation to 2,4-D involves the Msn2/Msn4-mediated transcriptional activation of SPI1, encoding a GPI anchored cell wall protein. Spi1p is required to reduce the intracellular pool of 2,4-D and the consequent intracellular acidification. The coordinate increased expression of PDR5 and SPI1 and resistance to enzymatic cell lysis, taking place during 2,4-D adaptation, strongly suggest the Spi1 role in restricting a futile cycle in which the acid diffuses into the cell, counteracting the inducible active expulsion of its anionic form, presumably through Pdr5.