The critical role of S-lactoylglutathione formation during methylglyoxal detoxification in Escherichia coli

Ertan Ozyamak (1) , Susan S Black (1) , Morag Maclean (1) , Claire Anne Walker (1) , Wendy Bartlett (1) , Samantha Miller (1) , Ian R Booth (2)

1 School of Medical Sciences
2 School of Medical Sciences

Survival of exposure to methylglyoxal (MG) in Gram-negative pathogens is largely dependent upon the operation of the glutathione dependent glyoxalase system, consisting of two enzymes, GlxI (gloA) and GlxII (gloB). In addition, the activation of the KefGB potassium efflux system is maintained closed by glutathione (GSH) and is activated by S lactoylGSH (SLG), the intermediate formed by GlxI and destroyed by GlxII. E. coli mutants lacking GlxI are known to be extremely sensitive to MG. In this study we demonstrate that a ΔgloB mutant is as tolerant of MG as the parent, despite having the same degree of inhibition of MG detoxification as a ΔgloA strain. Increased expression of GlxII from a multi copy plasmid sensitises E. coli to MG. Measurement of SLG pools, KefGB activity and cytoplasmic pH shows these parameters to be linked and to be very sensitive to changes in the activity of GlxI and GlxII. The SLG pool determines the activity of KefGB and the degree of acidification of the cytoplasm, which is a major determinant of the sensitivity to electrophiles. The data are discussed in terms of how cell fate is determined by the relative abundance of the enzymes and KefGB.

Mots clés: Life Sciences

Ertan Ozyamak, Susan S Black, Morag Maclean, Claire Anne Walker, Wendy Bartlett, et al.. The critical role of S-lactoylglutathione formation during methylglyoxal detoxification in Escherichia coli. Molecular Microbiology, 2010, 78 (6), pp.1577. ⟨10.1111/j.1365-2958.2010.07426.x⟩. ⟨hal-00589476⟩