title: KatG and KatE confer Acinetobacter resistance to hydrogen peroxide but sensitize bacteria to killing by phagocytic respiratory burst.
abstract: OBJECTIVE
  Catalase catalyzes the degradation of H2O2. Acinetobacter species have four predicted catalase genes, katA, katE, katG, and katX. The aims of the present study seek to determine which catalase(s) plays a predominant role in determining the resistance to H2O2, and to assess the role of catalase in Acinetobacter virulence.
  
  
  METHODS
  Mutants of Acinetobacter baumannii and Acinetobacter nosocomialis with deficiencies in katA, katE, katG, and katX were tested for sensitivity to H2O2, either by halo assays or by liquid culture assays. Respiratory burst of neutrophils, in response to A. nosocomialis, was assessed by chemiluminescence to examine the effects of catalase on the production of reactive oxygen species (ROS) in neutrophils. Bacterial virulence was assessed using a Galleria mellonella larva infection model.
  
  
  RESULTS
  The capacities of A. baumannii and A. nosocomialis to degrade H2O2 are largely dependent on katE. The resistance of both A. baumannii and A. nosocomialis to H2O2 is primarily determined by the katG gene, although katE also plays a minor role in H2O2 resistance. Bacteria lacking both the katG and katE genes exhibit the highest sensitivity to H2O2. While A. nosocomialis bacteria with katE and/or katG were able to decrease ROS production by neutrophils, these cells also induced a more robust respiratory burst in neutrophils than did cells deficient in both katE and katG. We also found that A. nosocomialis deficient in both katE and katG was more virulent than the wildtype A. nosocomialis strain.
  
  
  CONCLUSIONS
  Our findings suggest that inhibition of Acinetobacter catalase may help to overcome the resistance of Acinetobacter species to microbicidal H2O2 and facilitate bacterial disinfection.
authors: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Surgery, The Second Hospital of Shandong University, Jinan, Shandong, China.
authors: Daqing
authors: D
authors: Sun
authors: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Sara A
authors: SA
authors: Crowell
authors: Center of Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Christian M
authors: CM
authors: Harding
authors: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: P Malaka
authors: PM
authors: De Silva
authors: Center of Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Alistair
authors: A
authors: Harrison
authors: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Dinesh M
authors: DM
authors: Fernando
authors: Center of Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA.
authors: Kevin M
authors: KM
authors: Mason
authors: Center of Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.
authors: Estevan
authors: E
authors: Santana
authors: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Peter C
authors: PC
authors: Loewen
authors: Department of Microbiology, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Ayush
authors: A
authors: Kumar
authors: Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, Columbus, OH, USA; Department of Pediatrics, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: yusen.liu@nationwidechildrens.org.
authors: Yusen
authors: Y
authors: Liu
mesh_terms: D000150:Acinetobacter / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D000818:Animals; D002374:Catalase / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000502:physiology; D029968:Escherichia coli Proteins / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D010586:Phagocytes / Q000187:drug effects* / Q000201:enzymology; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology
chemical_list: D029968:Escherichia coli Proteins; D006861:Hydrogen Peroxide; C102664:hydroperoxidase II; D002374:Catalase; C051253:katG protein, E coli
keywords: Acinetobacter; Catalase; Hydrogen peroxide; KatE; KatG; Neutrophils; Reactive oxygen species