Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis.

In this study penicillin-binding proteins (PBPs) of Bacteroides fragilis and the resistance mechanisms of this micro-organism to 11 β-lactam antibiotics were analysed. The study focused on the role of PBP2Bfr and metallo-β-lactamase in the mechanism of resistance to imipenem. The mechanism of β-lactam resistance in B. fragilis was strain dependent. The gene encoding the orthologue of Escherichia coli PBP3 gene (pbpBBfr, which encodes the protein PBP2Bfr) was sequenced in five of the eight strains studied, along with the ccrA (cfiA) gene in strain 119, and their implications for resistance were examined. Differences were found in the amino-acid sequence of PBP2Bfr in strains AK-2 and 119, and the production of β-lactamases indicated that these differences may be involved in the mechanism of resistance to imipenem. In vitro binding competition assays with membrane extracts using imipenem indicated that the PBP that bound imipenem with the highest affinity was PBP2Bfr, and that increased affinity in strain 7160 may be responsible for the moderate susceptibility of this strain to imipenem. In the same way, the importance of the chromosomal class A β-lactamase CepA in the resistance mechanism of the B. fragilis strains NCTC 9344, 7160, 2013E, AK-4, 0423 and R-212 was studied. In these strains this is the principal resistance mechanism to antimicrobial agents studied other than imipenem.

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Penicillin-binding proteins of Bacteroides fragilis

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/14.2.197 ◽

1984 ◽

Vol 14 (2) ◽

pp. 197-200

Author(s):

GIUSEPPE A. BOTTA ◽

GAETANO PRIVITERA ◽

MARIA GRAZIA MENOZZI

Keyword(s):

Binding Proteins ◽

Bacteroides Fragilis ◽

Penicillin Binding Proteins

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Penicillin-Binding Proteins and the Mechanism of Action of Beta-Lactam Antibiotics1

Annual Review of Biochemistry ◽

10.1146/annurev.bi.52.070183.004141 ◽

1983 ◽

Vol 52 (1) ◽

pp. 825-869 ◽

Cited By ~ 386

Author(s):

D J Waxman ◽

J L Strominger

Keyword(s):

Mechanism Of Action ◽

Binding Proteins ◽

Beta Lactam ◽

Penicillin Binding Proteins

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Biochemical and genetical approaches to the mechanism of action of penicillin

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1980.0045 ◽

1980 ◽

Vol 289 (1036) ◽

pp. 273-283 ◽

Cited By ~ 64

Keyword(s):

Mechanism Of Action ◽

Binding Proteins ◽

Biological Effects ◽

Sodium Dodecyl ◽

Multiple Forms ◽

Considerable Effort ◽

Lethal Effects ◽

Penicillin Binding Proteins ◽

E Coli ◽

Peptidoglycan Synthesis

Since the discovery in 1965 that penicillin inhibits the transpeptidation reaction in peptidoglycan synthesis, a considerable effort has been put into the purification of enzymes that catalyse this reaction. This has resulted in the recognition that bacteria possess multiple forms of these penicillin-sensitive enzymes and has made it difficult to identify the precise target that penicillin inactivates to kill the organism. Recently penicillin-sensitive enzymes have been detected and studied as penicillin-binding proteins on sodium dodecyl sulphate polyacrylamide gels. The availability of this convenient method for identifying penicillin-sensitive enzymes has allowed biochemical and genetical approaches to be used to dissect their roles in the lethal effects of penicillin and other β-lactam antibiotics. Three penicillin-binding proteins (1B, 2 and 3) have been identified as killing targets for penicillin in Escherichia coli , whereas four other binding proteins are not implicated in the mechanism of action of the antibiotic. The complex biological effects that β-lactam antibiotics produce on the growth of E. coli can be explained by their interaction with the three killing targets. Progress in the correlation of penicillin-binding proteins with penicillin-sensitive enzymes and in the development of strains of E. coli that overproduce penicillin-binding proteins is discussed.

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