Staphylococcus aureus Glucose-Induced Biofilm Accessory Protein A (GbaA) Is a Monothiol-Dependent Electrophile Sensor.
Abstract
Staphylococcus aureus is a commensal pathogen that has evolved to protect itself from unfavorable conditions by forming complex community structures termed biofilms. The regulation of the formation of these structures is multifactorial and in S. aureus involves a number of transcriptional regulators. GbaA (glucose-induced biofilm accessory protein A) is a tetracycline repressor (TetR) family regulator that harbors two conserved Cys residues (C55 and C104) and impacts the regulation of formation of poly-N-acetylglucosamine-based biofilms in many methicillin-resistant S. aureus (MRSA) strains. Here, we show that GbaA-regulated transcription of a divergently transcribed operon in a MRSA strain can be induced by potent electrophiles, N-ethylmaleimide and methylglyoxal. Strikingly, induction of transcription in cells requires C55 or C104, but not both. These findings are consistent with in vitro small-angle X-ray scattering, chemical modification, and DNA operator binding experiments, which reveal that both reduced and intraprotomer (C55-C104) disulfide forms of GbaA have very similar overall structures and each exhibits a high affinity for the DNA operator, while DNA binding is strongly inhibited by derivatization of one or the oth...Continue Reading
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