CeBiTec Colloquium
Monday, February 13th 2017, 17 c.t.
G2-104, CeBiTec Building
Prof. Dr. Alan J. Slusarenko
Department of Plant Physiology, RWTH, Aachen
Cellular effects of the natural defence substance allicin from garlic
Allicin is a thiol-reactive sulfur-containing natural defence substance from garlic with a broad range of antimicrobial effects against prokaryotes and eukaryotes. Allicin is effective against several multiply antibiotic resistant (MDR) strains including methicillin-resistant Staphylococcus aureus (MRSA). Thus, allicin has potential for development as an alternative antibiotic in medicine and pesticide in agriculture. Allicin is a dose-dependent biocide and because it is a common foodstuff it is important to know what its effects on cells are. We have investigated allicin’s mode of action in cells with a variety of biochemical, physiological, genetic and cellular approaches with various bacteria and baker’s yeast as a model fungus. Allicin exposure causes a depletion of the cellular glutathione pool and S-allylmercapto modification of several proteins in cells, resulting in disulfide stress. In addition, the allicin molecule builds transient pores in lipid bilayers and works synergistically with antibiotics that target membranes. Using sub-lethal doses of allicin we have identified the yeast pYap1 transcription factor, which is the central regulator of the oxidative stress response, to be an allicin target. Allicin causes pYap1 to accumulate in the nucleus within 10 minutes of treatment and we used a systematic series of cysteine-to-alanine exchange mutants to identify which regulatory cysteine residues are involved in allicin activation of pYap1. Our data show that Yap1p is an important transcriptional regulator for the resistance of yeast cells to allicin, and that pYap1 activation occurs by direct modification of C-term cysteines as shown already for xenobiotic electrophiles, but here for the first time with a natural electrophilic oxidant.
Host: Prof. Dr. Karl-Josef Dietz