Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections.
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.
Bjarnsholt
Thomas
T
Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Jensen
Peter Østrup
PØ
Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
Rasmussen
Thomas B
TB
Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.
Christophersen
Lars
L
Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
Calum
Henrik
H
Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
Hentzer
Morten
M
Carlsberg Research Center, Biosector, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
Hougen
Hans-Petter
HP
Institute of Forensic Medicine, University of Copenhagen, DK-2100 Copenhagen Ø, Denmark.
Rygaard
Jørgen
J
Bartholin Instituttet, Kommune Hospitalet, Copenhagen, Denmark.
Moser
Claus
C
Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
Eberl
Leo
L
Department of Microbiology, University of Zürich, CH-8008 Zürich, Switzerland.
Høiby
Niels
N
Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
Givskov
Michael
M
Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark, DK-2800 Lyngby, Denmark.
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
D000900:Anti-Bacterial Agents; D010936:Plant Extracts