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

doi:10.1111/j.1600-0463.2009.02466.x

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

Department of Immunology and Microbiology

116 Citations (Scopus)

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 language	English
Journal	Acta Pathologica Microbiologica et Immunologica Scandinavica
Volume	117
Issue number	7
Pages (from-to)	537-46
Number of pages	10
ISSN	0903-4641
DOIs	https://doi.org/10.1111/j.1600-0463.2009.02466.x
Publication status	Published - 1 Jul 2009

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Van Gennip, M., Christensen, L. D., Alhede, M., Phipps, R., Jensen, P. Ø., Christophersen, L., Pamp, S. J., Moser, C., Mikkelsen, P. J., Koh, A. Y., Tolker-Nielsen, T., Pier, G. B., Høiby, N., Givskov, M., & Bjarnsholt, T. (2009). Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes. Acta Pathologica Microbiologica et Immunologica Scandinavica, 117(7), 537-46. https://doi.org/10.1111/j.1600-0463.2009.02466.x

Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes. / Van Gennip, Maria; Christensen, Louise Dahl; Alhede, Morten et al.

In: Acta Pathologica Microbiologica et Immunologica Scandinavica, Vol. 117, No. 7, 01.07.2009, p. 537-46.

Research output: Contribution to journal › Journal article › Research › peer-review

Van Gennip, M, Christensen, LD, Alhede, M, Phipps, R, Jensen, PØ, Christophersen, L, Pamp, SJ, Moser, C, Mikkelsen, PJ, Koh, AY, Tolker-Nielsen, T, Pier, GB, Høiby, N , Givskov, M & Bjarnsholt, T 2009, 'Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes', Acta Pathologica Microbiologica et Immunologica Scandinavica, vol. 117, no. 7, pp. 537-46. https://doi.org/10.1111/j.1600-0463.2009.02466.x

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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.",

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AU - Van Gennip, Maria

AU - Christensen, Louise Dahl

AU - Alhede, Morten

AU - Phipps, Richard

AU - Jensen, Peter Østrup

AU - Christophersen, Lars

AU - Pamp, Sünje Johanna

AU - Moser, Claus

AU - Mikkelsen, Per Jensen

AU - Koh, Andrew Y

AU - Tolker-Nielsen, Tim

AU - Pier, Gerald B

AU - Høiby, Niels

AU - Givskov, Michael

AU - Bjarnsholt, Thomas

PY - 2009/7/1

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N2 - 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.

AB - 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.

U2 - 10.1111/j.1600-0463.2009.02466.x

DO - 10.1111/j.1600-0463.2009.02466.x

M3 - Journal article

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JO - APMIS. Supplementum

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ER -

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

Abstract

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