Proteomic signatures uncover thiol-specific electrophile resistance mechanisms in Bacillus subtilis.
Proteomic and transcriptomics signatures are powerful tools for visualizing global changes in gene expression in bacterial cells after exposure to stress, starvation or toxic compounds. Based on the global expression profile and the dissection into specific regulons, this knowledge can be used to predict the mode of action for novel antimicrobial compounds. This review summarizes our recent progress of proteomic signatures in the model bacterium for low-GC Gram-positive bacteria Bacillus subtilis in response to the antimicrobial compounds phenol, catechol, salicylic acid, 2-methylhydroquinone (2-MHQ) and 6-brom-2-vinyl-chroman-4-on (chromanon). Catechol, 2-MHQ and diamide displayed a common mode of action, as revealed by the induction of the thiol-specific oxidative stress response. In addition, multiple dioxygenases/glyoxalases, azoreductases and nitroreductases were induced by thiol-reactive compounds that are regulated by two novel thiol-specific regulators, YodB and MhqR (YkvE), both of which contribute to electrophile resistance in B. subtilis. These novel thiol-stress-responsive mechanisms are highly conserved among Gram-positive bacteria and are thought to have evolved to detoxify quinone-like electrophiles.
Antelmann
Haike
H
Institute of Microbiology, Ernst-Moritz-Arndt-University of Greifswald, F.-L.-Jahn-Str. 15, D-17487 Greifswald, Germany. antelman@uni-greifswald.de
Hecker
Michael
M
Zuber
Peter
P
D001412:Bacillus subtilis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002396:Catechols / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003958:Diamide / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004790:Enzyme Induction / Q000187:drug effects; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000201:enzymology; D006873:Hydroquinones / Q000494:pharmacology; D009582:Nitrofurantoin / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D019800:Phenol / Q000494:pharmacology; D040901:Proteomics / Q000379:methods; D011809:Quinones / Q000494:pharmacology*; D018085:Regulon / Q000187:drug effects; D020156:Salicylic Acid / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000494:pharmacology*
C438644:2-methoxy-1,4-hydroquinone; C521295:6-brom-2-vinyl-chroman-4-on; D001426:Bacterial Proteins; D002396:Catechols; D002867:Chromones; D006873:Hydroquinones; D011809:Quinones; D013438:Sulfhydryl Compounds; D003958:Diamide; D019800:Phenol; D009582:Nitrofurantoin; C034221:catechol; D020156:Salicylic Acid