VanD-Type Vancomycin-Resistant Enterococcus faecium and Enterococcus faecalis
| Autor: | Florence Depardieu, Jan M. Bell, Mathias Kolbert, Patrice Courvalin, H. Pruul |
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| Rok vydání: | 2004 |
| Předmět: |
DNA
Bacterial Dipeptidases Transcription Genetic Enterococcus faecium Molecular Sequence Data Carboxypeptidases Enterococcus faecalis Microbiology chemistry.chemical_compound Plasmid Bacterial Proteins Mechanisms of Resistance Gene cluster medicine Computer Simulation Pharmacology (medical) Amino Acid Sequence Peptide Synthases DNA Primers Pharmacology biology Reverse Transcriptase Polymerase Chain Reaction Teicoplanin Structural gene Vancomycin Resistance Chromosomes Bacterial biology.organism_classification Molecular biology Electrophoresis Gel Pulsed-Field Housekeeping gene Infectious Diseases chemistry Multigene Family Peptidoglycan Plasmids medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 48:3892-3904 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.48.10.3892-3904.2004 |
| Popis: | Enterococcus faecium clinical isolates A902 and BM4538, which were resistant to relatively high levels of vancomycin (128 and 64 μg/ml, respectively) and to low levels of teicoplanin (4 μg/ml), and Enterococcus faecalis clinical isolates BM4539 and BM4540, which were resistant to moderate levels of vancomycin (16 μg/ml) and susceptible to teicoplanin (0.25 μg/ml), were studied. They were constitutively resistant by synthesis of peptidoglycan precursors ending with d -alanyl- d -lactate and harbored a chromosomal vanD gene cluster which was not transferable by conjugation to other enterococci. VanX D activity, which is not required in the absence of d -Ala- d -Ala, was low in the four strains, although none of the conserved residues was mutated; and the constitutive VanY D activity in the membrane fractions was inhibited by penicillin G. The mutations E 13 G in the region of d -alanine: d -alanine ligase (which is implicated in d -Ala1 binding in A902) and S 319 N of the serine involved in ATP binding in BM4538 and a 7-bp insertion at different locations in BM4539 and BM4540 (which led to putative truncated proteins) led to the production of an impaired enzyme and accounted for the lack of d -Ala- d -Ala-containing peptidoglycan precursors. The same 7-bp insertion in vanS D of BM4539 and BM4540 and a 1-bp deletion in vanS D of A902, which in each case led to a putative truncated and presumably nonfunctional protein, could account for the constitutive resistance. Strain BM4538, with a functional VanS D , had a G 140 E mutation in VanR D that could be responsible for constitutive glycopeptide resistance. This would represent the first example of constitutive van gene expression due to a mutation in the structural gene for a VanR transcriptional activator. Study of these four additional strains that could be distinguished on the basis of their various assortments of mutations confirmed that all VanD-type strains isolated so far have mutations in the ddl housekeeping gene and in the acquired vanS D or vanR D gene that lead to constitutive resistance to vancomycin. |
| Databáze: | OpenAIRE |
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