scholarly journals Complementation of the Essential Peptidoglycan Transpeptidase Function of Penicillin-Binding Protein 2 (PBP2) by the Drug Resistance Protein PBP2A in Staphylococcus aureus

2001 ◽  
Vol 183 (22) ◽  
pp. 6525-6531 ◽  
Author(s):  
Mariana G. Pinho ◽  
Sérgio R. Filipe ◽  
Hermı́nia de Lencastre ◽  
Alexander Tomasz
Keyword(s):  
Staphylococcus Aureus ◽  
Drug Resistance ◽  
Methicillin Resistance ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Resistance Protein ◽  
Essential Function ◽  
Direct Genetic Evidence ◽  
Block Growth ◽  
Lines Of Evidence

ABSTRACT The essential function of penicillin-binding protein 2 (PBP2) in methicillin-susceptible Staphylococcus aureus RN4220 was clearly established by placing the pbp2 gene under control of the inducible Pspac promoter; the resulting bacteria were unable to grow in the absence of inducer. In contrast, the deficit in PBP2 caused by inhibition of transcription of the pbp2gene did not block growth of a methicillin-resistant S. aureus strain expressing the extra penicillin-binding protein PBP2A, a protein of extraspecies origin that is central to the mechanism of methicillin resistance. Several lines of evidence indicate that the essential function of PBP2 that can be compensated for by PBP2A is the transpeptidase activity. This provides direct genetic evidence that PBP2A has transpeptidase activity.

scholarly journals Penicillin-binding protein 4 overproduction increases beta-lactam resistance in Staphylococcus aureus.

1996 ◽  
Vol 40 (9) ◽  
pp. 2121-2125 ◽  
Author(s):  
U U Henze ◽  
B Berger-Bächi
Keyword(s):  
Staphylococcus Aureus ◽  
Promoter Region ◽  
Methicillin Resistance ◽  
Binding Protein ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
In The Wild ◽  
Mutant Promoter

The Staphylococcus aureus mutant strain PVI selected in vitro for methicillin resistance overexpressed penicillin-binding protein (PBP) 4. In the wild-type parent strain the pbp4 gene was separated by 419 nucleotides from a divergently transcribed abcA locus coding for an ATP-binding cassette transporter. The mutant PVI was shown to have a deletion in the pbp4-abcA promoter region that affected pbp4 transcription but not expression of abcA. Introduction of the pbp4 gene plus the mutant promoter region into different genetic backgrounds revealed that PBP 4 overproduction was sufficient to increase in vitro-acquired methicillin resistance independently of other chromosomal genes. The role of the AbcA transporter in methicillin resistance remained unknown.

scholarly journals Ceftobiprole Is Superior to Vancomycin, Daptomycin, and Linezolid for Treatment of Experimental Endocarditis in Rabbits Caused by Methicillin-Resistant Staphylococcus aureus

2009 ◽  
Vol 54 (2) ◽  
pp. 610-613 ◽  
Author(s):  
P. Tattevin ◽  
L. Basuino ◽  
D. Bauer ◽  
B. A. Diep ◽  
H. F. Chambers
Keyword(s):  
Staphylococcus Aureus ◽  
Treatment Group ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Methicillin Resistance ◽  
Rabbit Model ◽  
Laboratory Strain ◽  
Penicillin Binding Protein ◽  
Beta Lactam ◽  
Methicillin Resistant ◽  
High Affinity

ABSTRACT Beta lactam agents are the most active drugs for the treatment of streptococci and methicillin-susceptible Staphylococcus aureus endocarditis. However, methicillin-resistant S. aureus (MRSA) is resistant to all beta lactam agents licensed to date, and alternative treatments are limited. Ceftobiprole is a novel broad-spectrum cephalosporin that binds with high affinity to PBP 2a, the penicillin binding protein that mediates the methicillin resistance of staphylococci and is active against MRSA. Ceftobiprole was compared to vancomycin, daptomycin, and linezolid in a rabbit model of MRSA aortic valve endocarditis caused by the homogeneously methicillin-resistant laboratory strain COL. Residual organisms in vegetations were significantly fewer in ceftobiprole-treated rabbits than in any other treatment group (P < 0.05 for each comparison). In addition, the numbers of organisms in spleens and in kidneys were significantly lower in ceftobiprole-treated rabbits than in linezolid- and vancomycin-treated animals (P < 0.05 for each comparison). Anti-MRSA beta lactam agents such as ceftobiprole may represent a significant therapeutic advance over currently available agents for the treatment of MRSA endocarditis.

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