title: Penicillin-binding proteins involved in high-level piperacillin resistance in Veillonella spp.
abstract: OBJECTIVE
  To investigate high-level piperacillin resistance in Veillonella spp. in the absence of beta-lactamase activity.
  
  
  METHODS
  Penicillin-binding protein (PBP) competition studies were conducted in Veillonella strains, with piperacillin MICs ranging from 0.5 to >128 mg/L and ampicillin MICs from 0.125 to 4 mg/L. Whole cell lysates were pre-incubated with piperacillin or ampicillin and post-labelled with [3H]benzylpenicillin.
  
  
  RESULTS
  PBP competition studies showed that the PBP with greatest affinity for penicillin and ampicillin had a molecular weight of approximately 66 kDa, and exhibited reduced binding of piperacillin in resistant strains.
  
  
  CONCLUSIONS
  This unusual focusing of different penicillins on one PBP may be the cause of selective mutants resulting from piperacillin MICs > 128 mg/L. In the absence of beta-lactamases, alterations in penicillin-binding were seen to be major contributors to high-level piperacillin resistance development.
authors.affiliation: Department of Medical Microbiology (G4), Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa. gnmbml@med.uovs.ac.za
authors.forename: Maria M
authors.initials: MM
authors.lastname: Theron
authors.forename: Marais N Janse
authors.initials: MN
authors.lastname: van Rensburg
authors.forename: Lynda J
authors.initials: LJ
authors.lastname: Chalkley
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D001426:Bacterial Proteins; D002352:Carrier Proteins / Q000378:metabolism*; D016905:Gram-Negative Bacterial Infections / Q000382:microbiology; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000378:metabolism*; D010403:Penicillin Resistance; D046915:Penicillin-Binding Proteins; D010406:Penicillins / Q000494:pharmacology*; D010458:Peptidyl Transferases; D010878:Piperacillin / Q000494:pharmacology*; D014678:Veillonella / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D000667:Ampicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase; D001618:beta-Lactamases; D010878:Piperacillin