title: Sub-inhibitory concentrations of ceftazidime and tobramycin reduce the quorum sensing signals of Pseudomonas aeruginosa.
abstract: OBJECTIVE
  Concentrations of antimicrobials below minimum inhibitory concentration (subMIC) may reduce the production by Pseudomonas aeruginosa of virulence factors such as elastase. We sought to determine whether the reduction in elastase production may be mediated by a reduction in acyl-homoserine lactones.
  
  
  METHODS
  Pseudomonas aeruginosa in broth was exposed to three conditions for ceftazidime and tobramycin: control, 6% MIC and 25% MIC. Elastase was assayed using elastin congo red. N-(3-Oxododecanoyl)-homoserine lactone (C12-HSL) and N-butyryl-homoserine lactone (C4-HSL) were assayed using biosensor Escherichia coli.
  
  
  RESULTS
  Elastase was unchanged with ceftazidime. Elastase was reduced by 16% at 6% MIC tobramycin and reduced by 70% at 25% MIC tobramycin (P<0.0001). As a percentage of control, C12-HSL was mean 69.4% (SEM 7.3%) at 6% MIC tobramycin, and 31.7% (3.3%) at 25% MIC tobramycin (P=0.0001). C12-HSL was 78.9% (5.3%) at 6% MIC ceftazidime and was 29.7% (1.8%) at 25% MIC ceftazidime (P=0.0001). Both ceftazidime and tobramycin were associated with reduced C4-HSL at 6% MIC and 25% MIC (P<0.03).
  
  
  CONCLUSIONS
  SubMIC tobramycin but not ceftazidime reduced elastase production by P. aeruginosa. In contrast, subMIC concentrations of both antimicrobials reduced C12-HSL and C4-HSL. It is unlikely that reduced HSL is the sole explanation for the reduction in elastase.
authors.affiliation: Adult Cystic Fibrosis Unit, The Prince Charles Hospital, Brisbane, Queensland, Australia. Luke_Garske@health.qld.gov.au
authors.forename: Luke A
authors.initials: LA
authors.lastname: Garske
authors.forename: Scott A
authors.initials: SA
authors.lastname: Beatson
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Leech
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Walsh
authors.forename: Scott C
authors.initials: SC
authors.lastname: Bell
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D010196:Pancreatic Elastase / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology; D015398:Signal Transduction / Q000187:drug effects*; D014031:Tobramycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D002442:Ceftazidime; D010196:Pancreatic Elastase; D014031:Tobramycin