Biomaterial Database

Mutations leading to increased levels of resistance to glycopeptide antibiotics in VanB-type enterococci. 1997

M Baptista, and F Depardieu, and P Reynolds, and P Courvalin, and M Arthur

Unité des Agents Antibactériens, Centre National de la Recherche Scientifique EP J0058, Institut Pasteur, Paris, France.

The vanB gene cluster mediates glycopeptide resistance by production of peptidoglycan precursors ending in the depsipeptide D-alanyl-D-lactate (D-Ala-D-Lac) instead of D-Ala-D-Ala found in susceptible enterococci. Synthesis of D-Ala-D-Lac and hydrolysis of D-Ala-D-Ala is controlled by the VanR(B)S(B) two-component regulatory system that activates transcription of the resistance genes in response to vancomycin but not to teicoplanin. Two substitutions (A3C-->G or D168-->Y) in the VanS(B) sensor kinase resulted in induction by teicoplanin, indicating that the N-terminal domain of the protein was involved in glycopeptide sensing. A substitution (T237-->K) located in the vicinity of the putative autophosphorylation site of VanS(B) (H233) was associated with a constitutive phenotype and affected a conserved residue known to be critical for the phosphatase activity of related kinases. A mutant producing an impaired host D-Ala:D-Ala ligase required vancomycin for growth, since D-Ala-D-Lac was only produced under inducing conditions. The ddl and vanS(B) mutations, alone or in combination, resulted in various resistance phenotypes that were determined by the amount of D-Ala-D-Ala and D-Ala-D-Lac incorporated into peptidoglycan precursors under different inducing 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
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010453	Peptide Synthases	Ligases that catalyze the joining of adjacent AMINO ACIDS by the formation of carbon-nitrogen bonds between their carboxylic acid groups and amine groups.	Peptide Synthetases,Acid-Amino-Acid Ligases,Acid Amino Acid Ligases,Ligases, Acid-Amino-Acid,Synthases, Peptide,Synthetases, Peptide
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
D014161	Transduction, Genetic	The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.	Genetic Transduction,Genetic Transductions,Transductions, Genetic
D016983	Enterococcus	A genus of gram-positive, coccoid bacteria consisting of organisms causing variable hemolysis that are normal flora of the intestinal tract. Previously thought to be a member of the genus STREPTOCOCCUS, it is now recognized as a separate genus.
D017334	Teicoplanin	Lipoglycopeptide antibiotic from Actinoplanes teichomyceticus active against gram-positive bacteria. It consists of five major components each with a different fatty acid moiety.	Teichomycin,Targocid,Teichomycin A2
D020713	Vancomycin Resistance	Nonsusceptibility of bacteria to the action of VANCOMYCIN, an inhibitor of cell wall synthesis.
D024881	Drug Resistance, Bacterial	The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).	Antibiotic Resistance, Bacterial,Antibacterial Drug Resistance