Loss of Cmk1 Ca2+-calmodulin-dependent protein kinase in yeast results in constitutive weak organic acid resistance, associated with a post-transcriptional activation of the Pdr12 ATP-binding cassette transporter

Yeast cells display an adaptive stress response when exposed to weak organi c acids at low pH, This adaptation is important in the spoilage of preserve d foods, as it allows growth in the presence of weak acid food preservative s. In Saccharomyces cerevisiae, this stress response leads to strong induct ion of the Pdr12 ATP-binding cassette (ABC) transporter, which catalyses th e active efflux of weak acid anions from the cytosol of adapted cells. S. c erevisiae cells lacking the Cmk1 isoform of Ca2+-calmodulin-dependent prote in kinase are intrinsically resistant to weak acid stress, in that they do not need to spend a long adaptive period in lag phase before resuming growt h after exposure to this stress. This resistance of the cmk1 mutant is Pdr1 2 dependent and, unlike with wild-type S, cerevisiae, cmk1 cells are capabl e of performing Pdr12-specific functions such as energy-dependent cellular extrusion of fluorescein and benzoate, However, they have neither higher PD R12 gene promoter activity nor higher Pdr12 protein levels. The increased P dr12 activity in cmk1 cells is therefore caused by Cmk1 exerting a negative posttranscriptional influence over the activity of the Pdr12 ABC transport er, a transporter protein that is constitutively expressed in low-pH yeast cultures. This is the first preliminary evidence that shows a protein kinas e, either directly or indirectly, regulating the activity of a yeast ABC tr ansporter.