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Microbiology 147 (2001), 1105-1113
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Microbiology (2001), 147, 1105-1113.
© 2001 Society for General Microbiology

Pathogenicity and Medical Microbiology

Pseudomonas aeruginosa mutations in lasI and rhlI quorum sensing systems result in milder chronic lung infection

Hong Wu1, Zhijun Song1,4, Michael Givskov2, Gerd Doring3, Dieter Worlitzsch3, Kalai Mathee4, Jørgen Rygaard5 and Niels Høiby1

Department of Clinical Microbiology, 9301 Rigshospitalet, Juliane Maries Vej 22, DK-2100, Copenhagen Ø, Denmark1
Institute of Microbiology, Technical University of Denmark, DK-2800, Lyngby, Denmark2
Hygiene Institute, University of Tübingen,D-72074, Tübingen, Germany3
Department of Biological Sciences, Florida International University, University Park, Miami, FL 33199, USA4
Bartholin Institute, Kommunehospitalet, Copenhagen, Denmark5

Author for correspondence: Hong Wu. Tel: +45 35456427. Fax: +45 35456412. e-mail: wuhong{at}get2net.dk

To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P. aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared. The rat model of P. aeruginosa lung infection was used in the present study. The rats were killed on days 3, 7, 14 and 28 after infection with the P. aeruginosa strains. The results showed that during the early stages of infection, the PAO1 double mutant induced a stronger serum antibody response, higher production of pulmonary interferon {gamma}, and more powerful blood polymorphonuclear leukocyte (PMN) chemiluminescence compared to its wild-type counterpart. On days 14 and 28 post-infection, significantly milder lung pathology, a reduction in the number of mast cells present in the lung foci, a reduced number of lung bacteria, and minor serum IgG and IgG1 responses but increased lung interferon {gamma} production were detected in the group infected with the PAO1 double mutant when compared with the PAO1-infected group. Delayed immune responses were observed in the PAO1-infected group and they might be associated with the production of virulence factors that are controlled by the quorum sensing systems. The conclusion of this study is that functional lasI and rhlI genes of P. aeruginosa PAO1 play a significant role during lung infection.

Keywords: lasI and rhlI, N-acylhomoserine lactones, chronic lung infection, cystic fibrosis, rat model

Abbreviations: AHL, N-acylhomoserine lactone; CF, cystic fibrosis; IFN-{gamma}, interferon {gamma}; IL, interleukin; LIMP, lung index of macroscopic pathology; MN, mononuclear leukocyte; p.i., post-infection; PMN, polymorphonuclear leukocyte; St-Ag, P. aeruginosa standard antigen




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