Target for bacteriostatic and bactericidal activities of beta-lactam antibiotics against Escherichia coli resides in different penicillin-binding proteins. 1995

G Satta, and G Cornaglia, and A Mazzariol, and G Golini, and S Valisena, and R Fontana
Istituto di Microbiologia, Università Cattolica del Sacro Cuore, Rome, Italy.

The relationship between cell-killing kinetics and penicillin-binding protein (PBP) saturation has been evaluated in the permeability mutant Escherichia coli DC2 in which the antimicrobial activity of beta-lactams has been described as being directly related to the extent of saturation of the PBP target(s). Saturation of a single PBP by cefsulodin (PBP 1s), mecillinam (PBP 2), and aztreonam (PBP 3) resulted in a slow rate of killing (2.5-, 1.5-, and 0.8-log-unit decreases in the number of CFU per milliliter, respectively, in 6 h). Saturation of two of the three essential PBPs resulted in a marked increase in the rate of killing, which reached the maximum value when PBPs 1s and 2 were simultaneously saturated by a combination of cefsulodin and mecillinam (4.7-log-unit decrease in the number of CFU per milliliter in 6 h). Inactivation of all three essential PBPs by the combination of cefsulodin, mecillinam, and aztreonam further increased the killing kinetics (5.5-log-unit decrease in the number of CFU per milliliter), and this was not significantly changed upon additional saturation of the nonessential PBPs 5 and 6 by cefoxitin. Similar relationships between PBP saturation and killing kinetics were obtained with imipenem and meropenem at concentrations which inhibited only one PBP (PBP 2), only two PBPs (PBP 1s and 2), or all three essential PBPs. Saturation of one or more PBPs also resulted in a different rate of bacteriolysis, the highest rate being obtained by the cefsulodin-mecillinam combination and by 5 micrograms of either imipenem or meropenem per ml. All of these conditions caused saturation of PBP 2 and saturation or extensive binding of PBP 1s. However, none of these conditions caused determined the fastest possible rate of killing, which occurred only when all three essential PBPs were saturated. It was concluded that the actual killing effect of beta-lactams is reflected by killing rates that approach the fastest possible rate for the given microorganism and that the targets for the bactericidal activity are precisely those PBPs whose saturation or binding occurs under conditions.

UI MeSH Term Description Entries
D008826 Microbial Sensitivity Tests Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses). Bacterial Sensitivity Tests,Drug Sensitivity Assay, Microbial,Minimum Inhibitory Concentration,Antibacterial Susceptibility Breakpoint Determination,Antibiogram,Antimicrobial Susceptibility Breakpoint Determination,Bacterial Sensitivity Test,Breakpoint Determination, Antibacterial Susceptibility,Breakpoint Determination, Antimicrobial Susceptibility,Fungal Drug Sensitivity Tests,Fungus Drug Sensitivity Tests,Sensitivity Test, Bacterial,Sensitivity Tests, Bacterial,Test, Bacterial Sensitivity,Tests, Bacterial Sensitivity,Viral Drug Sensitivity Tests,Virus Drug Sensitivity Tests,Antibiograms,Concentration, Minimum Inhibitory,Concentrations, Minimum Inhibitory,Inhibitory Concentration, Minimum,Inhibitory Concentrations, Minimum,Microbial Sensitivity Test,Minimum Inhibitory Concentrations,Sensitivity Test, Microbial,Sensitivity Tests, Microbial,Test, Microbial Sensitivity,Tests, Microbial Sensitivity
D010458 Peptidyl Transferases Acyltransferases that use AMINO ACYL TRNA as the amino acid donor in formation of a peptide bond. There are ribosomal and non-ribosomal peptidyltransferases. Peptidyl Transferase,Peptidyl Translocase,Peptidyl Translocases,Peptidyltransferase,Transpeptidase,Transpeptidases,Peptidyltransferases,Transferase, Peptidyl,Transferases, Peptidyl,Translocase, Peptidyl,Translocases, Peptidyl
D002267 Muramoylpentapeptide Carboxypeptidase Enzyme which catalyzes the peptide cross-linking of nascent CELL WALL; PEPTIDOGLYCAN. Carboxypeptidase Transpeptidase,Carboxypeptidase, Muramoylpentapeptide,Transpeptidase, Carboxypeptidase
D002352 Carrier Proteins Proteins that bind or transport specific substances in the blood, within the cell, or across cell membranes. Binding Proteins,Carrier Protein,Transport Protein,Transport Proteins,Binding Protein,Protein, Carrier,Proteins, Carrier
D004926 Escherichia coli A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc. Alkalescens-Dispar Group,Bacillus coli,Bacterium coli,Bacterium coli commune,Diffusely Adherent Escherichia coli,E coli,EAggEC,Enteroaggregative Escherichia coli,Enterococcus coli,Diffusely Adherent E. coli,Enteroaggregative E. coli,Enteroinvasive E. coli,Enteroinvasive Escherichia coli
D006602 Hexosyltransferases Enzymes that catalyze the transfer of hexose groups. EC 2.4.1.-.
D000900 Anti-Bacterial Agents Substances that inhibit the growth or reproduction of BACTERIA. Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001426 Bacterial Proteins Proteins found in any species of bacterium. Bacterial Gene Products,Bacterial Gene Proteins,Gene Products, Bacterial,Bacterial Gene Product,Bacterial Gene Protein,Bacterial Protein,Gene Product, Bacterial,Gene Protein, Bacterial,Gene Proteins, Bacterial,Protein, Bacterial,Proteins, Bacterial
D001433 Bacteriolysis Rupture of bacterial cells due to mechanical force, chemical action, or the lytic growth of BACTERIOPHAGES. Bacteriolyses
D046915 Penicillin-Binding Proteins Bacterial proteins that share the property of binding irreversibly to PENICILLINS and other ANTIBACTERIAL AGENTS derived from LACTAMS. The penicillin-binding proteins are primarily enzymes involved in CELL WALL biosynthesis including MURAMOYLPENTAPEPTIDE CARBOXYPEPTIDASE; PEPTIDE SYNTHASES; TRANSPEPTIDASES; and HEXOSYLTRANSFERASES. Penicillin-Binding Protein,Penicillin-Binding Protein 1,Penicillin-Binding Protein 1A,Penicillin-Binding Protein 1b,Penicillin-Binding Protein 2,Penicillin-Binding Protein 2a,Penicillin-Binding Protein 2b,Penicillin-Binding Protein 3,Penicillin-Binding Protein 4,Penicillin-Binding Protein 5,Penicillin-Binding Protein 6,Penicillin-Binding Protein 7,Penicillin-Binding Protein-2a,Peptidoglycan Synthetase,Penicillin Binding Protein,Penicillin Binding Protein 1,Penicillin Binding Protein 1A,Penicillin Binding Protein 1b,Penicillin Binding Protein 2,Penicillin Binding Protein 2a,Penicillin Binding Protein 2b,Penicillin Binding Protein 3,Penicillin Binding Protein 4,Penicillin Binding Protein 5,Penicillin Binding Protein 6,Penicillin Binding Protein 7,Penicillin Binding Proteins,Protein 1A, Penicillin-Binding,Protein 1b, Penicillin-Binding,Proteins, Penicillin-Binding,Synthetase, Peptidoglycan

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