Abstract
The low-affinity penicillin-binding protein (PBP) 5 is the main beta-lactam target and is responsible for resistance to this class of antibiotics in Enterococcus faecium. The PBP 5 variants of 15 clinical isolates (including 8 resistant to vancomycin) with different levels of beta-lactam resistance were analyzed. Most of the highly beta-lactam-resistant isolates produced small quantities of PBP 5 of low affinity. This was associated with particular amino acid substitutions: an Ala or Ile for Thr-499, a Glu for Val-629, and a Pro for Ser-667. A change of Met-485 to Thr or Ala (adjacent to the conserved SDN box) was observed in isolates with MICs of ampicillin of 64 or 128 microg/mL, respectively. In the 2 most resistant isolates, with MICs of ampicillin of 256 microg/mL, an additional Ser was present just after Ser-466. Thus, particular point mutations in PBP 5 and combinations thereof may lead to high-level beta-lactam resistance in E. faecium.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Ampicillin / pharmacology
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Bacterial Proteins*
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Carrier Proteins / chemistry
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Carrier Proteins / genetics*
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Carrier Proteins / metabolism
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Drug Resistance, Microbial
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Enterococcus faecium / drug effects*
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Enterococcus faecium / genetics*
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Enterococcus faecium / isolation & purification
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Genetic Variation
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Gram-Positive Bacterial Infections / microbiology
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Hexosyltransferases*
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Humans
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Imipenem / pharmacology
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Microbial Sensitivity Tests
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Molecular Sequence Data
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Muramoylpentapeptide Carboxypeptidase / chemistry
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Muramoylpentapeptide Carboxypeptidase / genetics*
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Muramoylpentapeptide Carboxypeptidase / metabolism
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Penicillin G / metabolism
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Penicillin G / pharmacology
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Penicillin Resistance / genetics
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Penicillin-Binding Proteins
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Peptidyl Transferases*
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Piperacillin / pharmacology
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Sequence Homology, Amino Acid
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Vancomycin / pharmacology
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beta-Lactam Resistance / genetics*
Substances
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Bacterial Proteins
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Carrier Proteins
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Penicillin-Binding Proteins
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Vancomycin
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Imipenem
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Ampicillin
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Peptidyl Transferases
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Hexosyltransferases
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Muramoylpentapeptide Carboxypeptidase
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Penicillin G
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Piperacillin