title: Combination of hypothiocyanite and lactoferrin (ALX-109) enhances the ability of tobramycin and aztreonam to eliminate Pseudomonas aeruginosa biofilms growing on cystic fibrosis airway epithelial cells.
abstract: OBJECTIVE
  Chelating iron may be a promising new therapy to eliminate Pseudomonas aeruginosa biofilms in the lungs of cystic fibrosis (CF) patients. Here, we investigate whether ALX-109 [a defined combination of an investigational drug containing lactoferrin (an iron-binding glycoprotein) and hypothiocyanite (a bactericidal agent)], alone and in combination with tobramycin or aztreonam, reduces P. aeruginosa biofilms grown on human CF airway epithelial cells.
  
  
  METHODS
  P. aeruginosa (PAO1 and six clinical isolates of Pseudomonas) biofilms grown at the apical surface of confluent monolayers of CF airway epithelial cells were treated with ALX-109, either alone or in combination with tobramycin or aztreonam. Bacterial cfu remaining after treatment were determined by plate counting.
  
  
  RESULTS
  ALX-109 alone reduced PAO1 biofilm formation, but had no effect on established biofilms. ALX-109 enhanced the ability of tobramycin and aztreonam to inhibit PAO1 biofilm formation and to reduce established PAO1 biofilms. ALX-109 and tobramycin were additive in disrupting established biofilms formed by six clinical isolates of P. aeruginosa obtained from the sputum of CF patients. Mucoid P. aeruginosa isolates were most susceptible to the combination of ALX-109 and tobramycin. In addition, ALX-109 also enhanced the ability of aztreonam to reduce established PAO1 biofilms.
  
  
  CONCLUSIONS
  Inhalation therapy combining hypothiocyanite and lactoferrin with TOBI(®) (tobramycin) or Cayston(®) (aztreonam) may be beneficial to CF patients by decreasing the airway bacterial burden of P. aeruginosa.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA sophie.m.marquis@gmail.com.
authors.forename: Sophie
authors.initials: S
authors.lastname: Moreau-Marquis
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Bonita
authors.initials: B
authors.lastname: Coutermarsh
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Stanton
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism*; D001398:Aztreonam / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development; D002478:Cells, Cultured; D015169:Colony Count, Microbial; D004338:Drug Combinations; D004357:Drug Synergism; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D007781:Lactoferrin / Q000378:metabolism*; D050296:Microbial Viability / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D013861:Thiocyanates / Q000378:metabolism*; D014031:Tobramycin / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013861:Thiocyanates; C014607:hypothiocyanite ion; D007781:Lactoferrin; D001398:Aztreonam; D014031:Tobramycin
keywords: OSCN−; P. aeruginosa; mucoviscidosis