title: Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa.
abstract: Quorum sensing (QS) denotes a density-dependent mode of inter-bacterial communication based on signal transmitter molecules. Active QS is present during chronic infections with the opportunistic pathogen Pseudomonas aeruginosa in immunocompromised patients. The authors have previously demonstrated a QS-regulated tolerance of biofilm bacteria to the antimicrobial properties of polymorphonuclear leukocytes (PMNs). The precise QS-regulated effect on the PMNs is, however, unknown. Incubation of human PMNs with supernatants from dense P. aeruginosa cultures showed that the QS-competent P. aeruginosa induced rapid necrosis of the PMNs. This mechanism was also observed in mouse lungs infected with P. aeruginosa, and in sputum obtained from P.-aeruginosa-infected patients with cystic fibrosis. Evidence is presented that the necrotic effect was caused by rhamnolipids, production of which is QS controlled. The results demonstrate the potential of the QS system to facilitate infections with P. aeruginosa by disabling the PMNs, which are a major first line of defence of the host. Furthermore, the study emphasizes the inhibition of QS as a target for the treatment of infections with P. aeruginosa.
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Peter Ø
authors.initials: PØ
authors.lastname: Jensen
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjarnsholt
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark.
authors.forename: Richard
authors.initials: R
authors.lastname: Phipps
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of 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: Henrik
authors.initials: H
authors.lastname: Calum
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Christoffersen
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Claus
authors.initials: C
authors.lastname: Moser
authors.affiliation: Centre for Biomolecular Sciences, University of Nottingham, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.affiliation: Copenhagen CF Center, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Tacjana
authors.initials: T
authors.lastname: Pressler
authors.affiliation: Centre for Biomedical Microbiology, BioCentrum, Technical University of Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Givskov
authors.affiliation: Department of Clinical Microbiology, Rigshospitalet, DK-2100 Copenhagen Ø, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Høiby
mesh_terms: D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006017:Glycolipids / Q000096:biosynthesis* / Q000633:toxicity*; D006801:Humans; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000276:immunology*; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D053038:Quorum Sensing; D013183:Sputum / Q000276:immunology / Q000382:microbiology; D014774:Virulence / Q000502:physiology*
chemical_list: D006017:Glycolipids; C418382:rhamnolipid