An oxidation-sensing mechanism is used by the global regulator MgrA in Staphylococcus aureus

Speaker: 蘇聖淵                                    Time: 2006 / 12 / 20  14:10~15:00

Commentator: 莊偉哲 老師                 Place: 601 room

Abstract:

Staphylococcus aureus is a well-known pathogenic bacterium that has many virulent factors to contribute infection. In earlier research, it has seen the MgrA, a DNA-binding protein, controlled 350 genes expression (1). Here, the authors elucidate how the MgrA participate in genes regulation, like norA transporter gene, as S. aureus suffers the oxidative-stress by Quinolones orVancomycins chemotherapy (2). First, they used amino acid sequence-alignment and crystallography to understand MgrA is a homodimer (solved at 2.86 Å) and a unique cysteine residue at the interface of protein. Base on these data they considered the classification is homolog of the MarR family (multiple-antimicrobial resistance proteins) (3) and physiological function is similar toOhrR protein, an organic hydroperoxide resistance regulator (4). In electrophoretic mobility shift assay, they found MgrA binds to DNA and cysteine oxidation leads to dissociate directly. Also, they compared drug-resistance ability between wild type strain and mgrA mutant in basal or oxidation state. The mgrA mutants are more survival and resistant in basal or oxidative condition. After all, this oxidation-sensing will initiate the signaling pathways to protect bacterium itself and turn on antibiotics resistance to quinolones and vancomycins.
 

References:

1. T.T. Luong, P.M. Dunman, Ellen Murphy, S.J. Projan and C.Y. Lee; Transcription profiling of the mgrA regulon in Staphylococcus aureus. 2006, J.Bacteriol. 188: 1899-1910.

2. Q.C. Truong-Bolduc, P.M. Dumman, J. Strahilevitz, S.J. Projan and D.C. Hooper; MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. 2005, J.Bacteriol. 187: 2395-2405

3. M.N. Aleshun, S.B. Levy, T.R. Mealy, B.A. Seaton and J.F. Head; The crystal structure of MarR, a regulator of multiple antibiotic resistances, at 2.3 Å resolution. 2001, Nat. Structural Bio.8: 710-714.

4. M. Hong, M. Fuangthong, J.D. Helmann and R.G. Brennan; Structure of an OhrR-ohrA operator complex reveals the DNA binding mechanism of the MarR family. 2005, Mol Cell, 20: 131-141.