Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes

• Published in: APMIS : acta pathologica, microbiologica et immunologica Scandinavica Vol. 117; no. 7; pp. 537 - 546
• Main Authors: VAN GENNIP, MARIA, CHRISTENSEN, LOUISE DAHL, ALHEDE, MORTEN, PHIPPS, RICHARD, JENSEN, PETER ØSTRUP, CHRISTOPHERSEN, LARS, PAMP, SÜNJE JOHANNA, MOSER, CLAUS, MIKKELSEN, PER JENSEN, KOH, ANDREW Y, TOLKER-NIELSEN, TIM, PIER, GERALD B, HØIBY, NIELS, GIVSKOV, MICHAEL, BJARNSHOLT, THOMAS
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.07.2009; Blackwell Publishing Ltd; Blackwell
• Subjects: Animals; Bacteriology; biofilm; Biofilms; Biological and medical sciences; Colony Count, Microbial; DNA, Bacterial - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Silencing; Glycolipids - antagonists & inhibitors; Glycolipids - biosynthesis; Glycolipids - genetics; Glycolipids - immunology; Infectious diseases; Medical sciences; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; mouse models; Neutrophils - immunology; PMN; Point Mutation; Prostheses and Implants - microbiology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa - metabolism; Pseudomonas Infections - blood; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Quorum Sensing - genetics; Quorum Sensing - physiology; Rhamnolipid; Pseudomonadales; mouse models; Animal model; Microbiology; Rhamnolipid; PMN; Immunology; Gene; Biofilm; Bacteria; Pseudomonadaceae; Pseudomonas aeruginosa; Neutrophil
• ISSN: 0903-4641; 1600-0463
• DOI: 10.1111/j.1600-0463.2009.02466.x

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.