On the Transcriptional Regulation of Methicillin Resistance
On the Transcriptional Regulation of Methicillin Resistance
复制标题
甲氧西林耐药的转录调控
DOI：
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发表时间：
2004
影响因子：
4.8
通讯作者：
F. Gomis
中科院分区：
文献类型：
--
作者：
R. García;G. Mallorquí;A. Marrero;J. Potempa;M. Coll;F. Gomis
Bacterial resistance to antibiotics poses a serious worldwide public health problem due to the high morbidity and mortality caused by infectious diseases. Most hospital-onset infections are associated with methicillin-resistant Staphylococcus aureus (MRSA) strains that have acquired multiple drug resistance to β-lactam antibiotics. In a response to antimicrobial stress, nearly all clinical MRSA isolates produce β-lactamase (BlaZ) and a penicillin-binding protein with low affinity for β-lactam antibiotics (PBP2a, also known as PBP2′ or MecA). Both effectors are regulated by homologous signal transduction systems consisting of a sensor/transducer and a transcriptional repressor. MecI (methicillin repressor) blocks mecA but also blaZ transcription and that of itself and the co-transcribed sensor/transducer. The structure of MecI in complex with a cognate operator double-stranded DNA reveals a homodimeric arrangement with a novel C-terminal spiral staircase dimerization domain responsible for dimer integrity. Each protomer interacts with the DNA major groove through a winged helix DNA-binding domain and specifically recognizes the nucleotide sequence 5′-Gua-Thy-Ade-X-Thy-3′. This results in an unusual convex bending of the DNA helix. The structure of this first molecular determinant of methicillin resistance in complex with its target DNA provides insights into its regulatory mechanism and paves the way for new antimicrobial strategies against MRSA.
DOI：
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发表时间：
1994-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
W. Shi;J. Wu;B. Rosen
通讯作者：
W. Shi;J. Wu;B. Rosen