title: Paradoxical effect of Klebsiella pneumoniae OmpK36 porin deficiency.
abstract: OBJECTIVE
  To evaluate the effect of defined mutations in the major OmpK35 and OmpK36 porins in Klebsiella pneumoniae on the activity of two common plasmid-mediated AmpC enzymes.
  
  
  METHODS
  Naturally occurring conjugative plasmids containing bla(DHA-1) and bla(CMY-2) were obtained from K. pneumoniae isolates in western Sydney. These were moved into K. pneumoniae ATCC13883 and isogenic porin knockouts Kp885 (DeltaompK35) and Kp886 (DeltaompK36), created by homologous recombination of kanamycin resistance cartridges into the specified genes, and their antimicrobial susceptibilities compared.
  
  
  RESULTS
  beta-lactam resistance was greater in the presence of CMY-2-containing plasmids than DHA-1-containing plasmids, and higher in K. pneumoniae than Escherichia coli. Neither cefepime nor imipenem resistance was observed, and DHA-mediated cefotaxime and ticarcillin/clavulanate resistance was unexpectedly reduced from 8-24 (CTX) and >256 (TIM) mg/L in Kp13883 to 1-2 (CTX) and 32-48 mg/L (TIM) in the isogenic DeltaompK36 porin knockout Kp886.
  
  
  CONCLUSIONS
  AmpC plasmids in particular are an important cause of transmissible resistance to ticarcillin/clavulanate in K. pneumoniae, but probably not in E. coli. Single knockouts of OmpK35 and OmpK36 porins in K. pneumoniae do not significantly increase antibiotic resistance in K. pneumoniae, and a paradoxical lowering of resistance to CTX and TIM is seen with deletion of ompK36. This has potentially important clinical implications.
authors.affiliation: Centre for Infectious Diseases and Microbiology, University of Sydney, Westmead Hospital, Sydney, NSW, Australia.
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Jiang
authors.forename: Bjorn A
authors.initials: BA
authors.lastname: Espedido
authors.forename: Sally R
authors.initials: SR
authors.lastname: Partridge
authors.forename: Lee C
authors.initials: LC
authors.lastname: Thomas
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Iredell
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D055786:Gene Knockout Techniques; D007711:Klebsiella pneumoniae / Q000201:enzymology / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010957:Plasmids; D016133:Polymerase Chain Reaction; D018272:Porins / Q000172:deficiency / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D001426:Bacterial Proteins; C092233:OmpK36 protein, Klebsiella pneumoniae; D018272:Porins; C048795:AmpC beta-lactamases; D001618:beta-Lactamases