Genome-wide responses to carbonyl electrophiles in Bacillus subtilis: control of the thiol-dependent formaldehyde dehydrogenase AdhA and cysteine proteinase YraA by the MerR-family regulator YraB (AdhR).
Quinones and alpha,beta-unsaturated carbonyls are naturally occurring electrophiles that target cysteine residues via thiol-(S)-alkylation. We analysed the global expression profile of Bacillus subtilis to the toxic carbonyls methylglyoxal (MG) and formaldehyde (FA). Both carbonyl compounds cause a stress response characteristic for thiol-reactive electrophiles as revealed by the induction of the Spx, CtsR, CymR, PerR, ArsR, CzrA, CsoR and SigmaD regulons. MG and FA triggered also a SOS response which indicates DNA damage. Protection against FA is mediated by both the hxlAB operon, encoding the ribulose monophosphate pathway for FA fixation, and a thiol-dependent formaldehyde dehydrogenase (AdhA) and DJ-1/PfpI-family cysteine proteinase (YraA). The adhA-yraA operon and the yraC gene, encoding a gamma-carboxymuconolactone decarboxylase, are positively regulated by the MerR-family regulator, YraB(AdhR). AdhR binds specifically to its target promoters which contain a 7-4-7 inverted repeat (CTTAAAG-N4-CTTTAAG) between the -35 and -10 elements. Activation of adhA-yraA transcription by AdhR requires the conserved Cys52 residue in vivo. We speculate that AdhR is redox-regulated via thiol-(S)-alkylation by aldehydes and that AdhA and YraA are specifically involved in reduction of aldehydes and degradation or repair of damaged thiol-containing proteins respectively.
Nguyen
Thi Thu Huyen
TT
Institute for Microbiology, Ernst-Moritz-Arndt-University of Greifswald, D-17487 Greifswald, Germany.
Eiamphungporn
Warawan
W
Mäder
Ulrike
U
Liebeke
Manuel
M
Lalk
Michael
M
Hecker
Michael
M
Helmann
John D
JD
Antelmann
Haike
H
D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016000:Cluster Analysis; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D009876:Operon; D011401:Promoter Regions, Genetic; D020543:Proteome / Q000378:metabolism; D011765:Pyruvaldehyde / Q000494:pharmacology; D012329:RNA, Bacterial / Q000235:genetics; D018085:Regulon; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D020543:Proteome; D012329:RNA, Bacterial; D005557:Formaldehyde; D011765:Pyruvaldehyde; C020145:formaldehyde dehydrogenase (glutathione); D000445:Aldehyde Oxidoreductases; D003546:Cysteine Endopeptidases