title: Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.
abstract: The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated. P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology and cytokine production were used as indicators. The garlic treatment initially provoked a higher degree of inflammation, and significantly improved clearing of the infecting bacteria. The results indicate that a QS-inhibitory extract of garlic renders P. aeruginosa sensitive to tobramycin, respiratory burst and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections.
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjarnsholt
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Peter Østrup
authors.initials: PØ
authors.lastname: Jensen
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Rasmussen
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Christophersen
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Calum
authors.affiliation: Carlsberg Research Center, Biosector, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Hentzer
authors.affiliation: Institute of Forensic Medicine, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Hans-Petter
authors.initials: HP
authors.lastname: Hougen
authors.affiliation: Bartholin Instituttet, Kommune Hospitalet, Copenhagen, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rygaard
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Moser
authors.affiliation: Department of Microbiology, University of Zürich, CH-8008 Zürich, Switzerland.
authors.forename: Leo
authors.initials: L
authors.lastname: Eberl
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000382:microbiology; D005737:Garlic / Q000737:chemistry*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D010936:Plant Extracts