Interaction of BlaI, the repressor for the β‐lactamase gene of Bacillus licheniformis, with the blaP and blaI promoters

Grossman, Matthew J.; Curran, Ivan; Lampen, J. O.

doi:10.1016/0014-5793(89)80258-3

Cited by 6 publications

(6 citation statements)

References 12 publications

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“…We therefore conclude that other members of the MecI/BlaI repressor family probably contact their cognate operators and those related ( Fig. 2A) (16,47,48), bla from S. aureus (13,29), and mec from MRSA (11,12,29). In each case, the promoter regions affected are indicated, as well as the GenBank TM sequence accession numbers (in parentheses) and the position within the nucleotide sequence.…”

Section: Structure Of Methicillin Repressor Within the Complex-likementioning

confidence: 82%

On the Transcriptional Regulation of Methicillin Resistance

García‐Castellanos

Mallorqui-Fernandez

Marrero

et al. 2004

Journal of Biological Chemistry

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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 ␤-lactam antibiotics. In a response to antimicrobial stress, nearly all clinical MRSA isolates produce ␤-lactamase (BlaZ) and a penicillin-binding protein with low affinity for ␤-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 doublestranded 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.

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Section: Structure Of Methicillin Repressor Within the Complex-likementioning

confidence: 82%

On the Transcriptional Regulation of Methicillin Resistance

García‐Castellanos

Mallorqui-Fernandez

Marrero

et al. 2004

Journal of Biological Chemistry

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“…le. brane receptor, BlaRl, binds a,-lactam compound and transmits a signal to the cytoplasm that relieves repression by Blal of the 13-lactamase promoter. Mutations affecting blaI cause high-level constitutive,-lactamase synthesis (8,16,30).…”

Section: Resultsmentioning

confidence: 99%

“…RN24, derived from RN11, is a constitutive, high-level producer of ,B-lactamase because of a mutation in the 3-lactamase repressor (blal) gene (8,16). RN6390B is a wild-type (agr+) strain, RN6911 is an agr null strain (10,17), and RN6734 is a derivative of RN6390B that does not produce beta-hemolysin because of lysogenization with phage 413, which inserts within the beta-hemolysin structural gene (6).…”

Section: Methodsmentioning

confidence: 99%

Glycerol monolaurate inhibits the production of beta-lactamase, toxic shock toxin-1, and other staphylococcal exoproteins by interfering with signal transduction

Projan¹,

Brown-Skrobot²,

Schlievert³

et al. 1994

J Bacteriol

143

136

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Glycerol monolaurate (GML) is a naturally occurring surfactant that is used widely as an emulsifier in the food and cosmetics industries and is generally regarded as lacking in important biological activities. The recent observation that it inhibits the production of staphylococcal toxic shock toxin-i (P. M. Schlievert, J. R. Deringer, M. H. Kim, S. J. Projan, and R P. Novick, Antimicrob. Agents Chemother. 36:626-631, 1992) is therefore rather surprising and raises the interesting question of how such a compound might interact with cells. In this report, we show that GML inhibits the synthesis of most staphylococcal toxins and other exoproteins and that it does so at the level of transcription. We find that GML blocks the induction but not the constitutive synthesis of ,3-lactamase, suggesting that it acts by interfering with signal transduction.

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“…In this regulatory system PenI binds to three operators within the region containing the divergent promoters for penI and penP (Grossman and Lampen, 1987;Himeno et al, 1986;Salerno and Lampen, 1988). PenI represses penP by preventing the initiation or elongation of the mRNA and similarly the synthesis of PenI is autoregulated (Wittman and Wong, 1988;Grossman et al, 1989). It has been shown that PenI is present as a dimer in solution, that the DNA-binding function is located near the N-terminus and that the dimerization function is in the C-terminal region (Wittman et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Studies of the repressor (BlaI) of β‐lactamase synthesis in Staphylococcus aureus

Gregory

Lewis

Curnock

et al. 1997

Molecular Microbiology

103

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SummaryPurified BlaI, the putative repressor of the ␤-lactamase operon in Staphylococcus aureus, binds specifically to two regions of dyad symmetry (operators) located in the blaZ-blaR1 intergenic region. BlaI binds with similar affinity to the two regions and to the related sequence upstream of the mec gene found in methicillin-resistant strains of S. aureus, providing physical evidence for the cross-talk previously observed between these systems. A change from a lysine in the N-terminus of BlaI to an alanine or deletion of the C-terminal 23 amino acids severely reduces its DNA-binding ability, demonstrating the functional importance of both the N-and C-termini. An operator DNA-protein complex observed with crude cell lysates from repressed cells, indistinguishable from that observed with purified BlaI, was eliminated by induction of the ␤-lactamase operon. Furthermore, BlaI is proteolytically cleaved in response to the addition of inducer in a blaR1-dependent manner, providing primary evidence for the molecular basis of induction. Thus, BlaI is shown to be the repressor of the ␤-lactamase system.

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Interaction of BlaI, the repressor for the β‐lactamase gene of Bacillus licheniformis, with the blaP and blaI promoters

Cited by 6 publications

References 12 publications

On the Transcriptional Regulation of Methicillin Resistance

On the Transcriptional Regulation of Methicillin Resistance

Glycerol monolaurate inhibits the production of beta-lactamase, toxic shock toxin-1, and other staphylococcal exoproteins by interfering with signal transduction

Studies of the repressor (BlaI) of β‐lactamase synthesis in Staphylococcus aureus

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