title: In Vivo Efficacy of Antimicrobials against Biofilm-Producing Pseudomonas aeruginosa.
abstract: Patients suffering from cystic fibrosis (CF) are commonly affected by chronic Pseudomonas aeruginosa biofilm infections. This is the main cause for the high disease severity. In this study, we demonstrate that P. aeruginosa is able to efficiently colonize murine solid tumors after intravenous injection and to form biofilms in this tissue. Biofilm formation was evident by electron microscopy. Such structures could not be observed with transposon mutants, which were defective in biofilm formation. Comparative transcriptional profiling of P. aeruginosa indicated physiological similarity of the bacteria in the murine tumor model and the CF lung. The efficacy of currently available antibiotics for treatment of P. aeruginosa-infected CF lungs, such as ciprofloxacin, colistin, and tobramycin, could be tested in the tumor model. We found that clinically recommended doses of these antibiotics were unable to eliminate wild-type P. aeruginosa PA14 while being effective against biofilm-defective mutants. However, colistin-tobramycin combination therapy significantly reduced the number of P. aeruginosa PA14 cells in tumors at lower concentrations. Hence, we present a versatile experimental system that is providing a platform to test approved and newly developed antibiofilm compounds.
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany vinay.pawar@helmholtz-hzi.de.
authors.forename: Vinay
authors.initials: V
authors.lastname: Pawar
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Uliana
authors.initials: U
authors.lastname: Komor
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kasnitz
authors.affiliation: Molecular Bacteriology, Twincore, Centre for Clinical and Experimental Infection Research, Hannover, Germany.
authors.forename: Piotr
authors.initials: P
authors.lastname: Bielecki
authors.affiliation: Mouse Pathology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.affiliation: Biofilm Centre, German Heart Institute Berlin, Berlin, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Gocht
authors.affiliation: Biofilm Centre, German Heart Institute Berlin, Berlin, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Moter
authors.affiliation: Central Facility for Microscopy, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Molecular Bacteriology, Twincore, Centre for Clinical and Experimental Infection Research, Hannover, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Häussler
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D045744:Cell Line, Tumor; D003091:Colistin / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000188:drug therapy / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D008171:Lung Diseases / Q000188:drug therapy / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests / Q000379:methods; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D014031:Tobramycin / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D014031:Tobramycin; D003091:Colistin