Penicillin-binding protein 5 sequence alterations in clinical isolates of Enterococcus faecium with different levels of beta-lactam resistance.
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.
Rybkine
T
T
L.R.M.A. UFR Broussais-Hôtel-Dieu et UFR Pitié-Salpétrière, Université Paris VI, France.
Mainardi
J L
JL
Sougakoff
W
W
Collatz
E
E
Gutmann
L
L
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000667:Ampicillin / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D014644:Genetic Variation; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006602:Hexosyltransferases; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D002267:Muramoylpentapeptide Carboxypeptidase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D010400:Penicillin G / Q000378:metabolism / Q000494:pharmacology; D010403:Penicillin Resistance / Q000235:genetics; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D010878:Piperacillin / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D014640:Vancomycin / Q000494:pharmacology; D018440:beta-Lactam Resistance / Q000235:genetics*
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D014640:Vancomycin; D015378:Imipenem; D000667:Ampicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D010400:Penicillin G; D010878:Piperacillin