title: Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes.
abstract: Many of the virulence factors produced by the opportunistic human pathogen Pseudomonas aeruginosa are quorum-sensing (QS) regulated. Among these are rhamnolipids, which have been shown to cause lysis of several cellular components of the human immune system, e.g. monocyte-derived macrophages and polymorphonuclear leukocytes (PMNs). We have previously shown that rhamnolipids produced by P. aeruginosa cause necrotic death of PMNs in vitro. This raises the possibility that rhamnolipids may function as a 'biofilm shield'in vivo, which contributes significantly to the increased tolerance of P. aeruginosa biofilms to PMNs. In the present study, we demonstrate the importance of the production of rhamnolipids in the establishment and persistence of P. aeruginosa infections, using an in vitro biofilm system, an intraperitoneal foreign-body model and a pulmonary model of P. aeruginosa infections in mice. Our experimental data showed that a P. aeruginosa strain, unable to produce any detectable rhamnolipids due to an inactivating mutation in the single QS-controlled rhlA gene, did not induce necrosis of PMNs in vitro and exhibited increased clearance compared with its wild-type counterpart in vivo. Conclusively, the results support our model that rhamnolipids are key protective agents of P. aeruginosa against PMNs.
authors: Institute of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors: Maria
authors: M
authors: Van Gennip
authors: Louise Dahl
authors: LD
authors: Christensen
authors: Morten
authors: M
authors: Alhede
authors: Richard
authors: R
authors: Phipps
authors: Peter Østrup
authors: PØ
authors: Jensen
authors: Lars
authors: L
authors: Christophersen
authors: Sünje Johanna
authors: SJ
authors: Pamp
authors: Claus
authors: C
authors: Moser
authors: Per Jensen
authors: PJ
authors: Mikkelsen
authors: Andrew Y
authors: AY
authors: Koh
authors: Tim
authors: T
authors: Tolker-Nielsen
authors: Gerald B
authors: GB
authors: Pier
authors: Niels
authors: N
authors: Høiby
authors: Michael
authors: M
authors: Givskov
authors: Thomas
authors: T
authors: Bjarnsholt
mesh_terms: D000818:Animals; D018441:Biofilms; D015169:Colony Count, Microbial; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006017:Glycolipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D017354:Point Mutation; D019736:Prostheses and Implants / Q000382:microbiology; D011552:Pseudomonas Infections / Q000097:blood / Q000276:immunology / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology
chemical_list: D004269:DNA, Bacterial; D006017:Glycolipids; C418382:rhamnolipid