TY - JOUR
T1 - Proteomic signatures uncover thiol-specific electrophile resistance mechanisms in Bacillus subtilis
AU - Antelmann, Haike
AU - Hecker, Michael
AU - Zuber, Peter
N1 - Funding Information:
This work was supported by grants from the Deutsche Forschungsgemeinschaft, the Bundesministerium für Bildung und Forschung (BACELL-SysMo 031397A), the Fonds der Chemischen Industrie, the Bildungsministerium of Mecklenburg-Vorpommern and European Union grants BACELL-Health (LSHG-CT-2004-503468) and BACELL-BaSysBio (LSHG-CT-2006-037469) to Michael Hecker, as well as by grant GM45898 from the National Institutes of Health and grant from the Medical Research Foundation of Oregon to Peter Zuber. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - Bacillus subtilis
KW - Electrophile resistance
KW - MhqR
KW - Proteomic signature
KW - Thiol
KW - YodB
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U2 - 10.1586/14789450.5.1.77
DO - 10.1586/14789450.5.1.77
M3 - Review article
C2 - 18282125
AN - SCOPUS:39649108459
SN - 1478-9450
VL - 5
SP - 77
EP - 90
JO - Expert Review of Proteomics
JF - Expert Review of Proteomics
IS - 1
ER -