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

Maria Van Gennip, Louise Dahl Christensen, Morten Alhede, Richard Phipps, Peter Østrup Jensen, Lars Christophersen, Sünje Johanna Pamp, Claus Moser, Per Jensen Mikkelsen, Andrew Y. Koh, Tim Tolker-Nielsen, Gerald B. Pier, Niels HØiby, Michael Givskov, Thomas Bjarnsholt

Research output: Contribution to journalArticle

98 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)537-546
Number of pages10
JournalAPMIS
Volume117
Issue number7
DOIs
Publication statusPublished - Jul 2009

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Keywords

  • Biofilm
  • Mouse models
  • PMN
  • Pseudomonas aeruginosa
  • Rhamnolipid

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Microbiology (medical)
  • Immunology and Allergy

Cite this

Van Gennip, M., Christensen, L. D., Alhede, M., Phipps, R., Jensen, P. Ø., Christophersen, L., ... Bjarnsholt, T. (2009). Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes. APMIS, 117(7), 537-546. https://doi.org/10.1111/j.1600-0463.2009.02466.x