Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Acta Pathologica Microbiologica et Immunologica Scandinavica |
| Vol/bind | 117 |
| Udgave nummer | 7 |
| Sider (fra-til) | 537-46 |
| Antal sider | 10 |
| ISSN | 0903-4641 |
| DOI | |
| Status | Udgivet - 1 jul. 2009 |
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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; 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.
I: Acta Pathologica Microbiologica et Immunologica Scandinavica, Bind 117, Nr. 7, 01.07.2009, s. 537-46.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
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TY - JOUR
T1 - Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes
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
Y1 - 2009/7/1
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
C2 - 19594494
VL - 117
SP - 537
EP - 546
JO - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
JF - A P M I S. Acta Pathologica, Microbiologica et Immunologica Scandinavica
SN - 0903-4641
IS - 7
ER -