Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa
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Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. / Jensen, Peter Østrup; Bjarnsholt, Thomas; Phipps, Richard; Rasmussen, Thomas B; Calum, Henrik; Christoffersen, Lars; Moser, Claus; Williams, Paul; Pressler, Tacjana; Givskov, Michael; Høiby, Niels.
In: Microbiology, Vol. 153, No. Pt 5, 2007, p. 1329-38.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa
AU - Jensen, Peter Østrup
AU - Bjarnsholt, Thomas
AU - Phipps, Richard
AU - Rasmussen, Thomas B
AU - Calum, Henrik
AU - Christoffersen, Lars
AU - Moser, Claus
AU - Williams, Paul
AU - Pressler, Tacjana
AU - Givskov, Michael
AU - Høiby, Niels
N1 - Keywords: Animals; Cell Death; Cell Survival; Cells, Cultured; Cystic Fibrosis; Disease Models, Animal; Female; Glycolipids; Humans; Lung; Mice; Mice, Inbred BALB C; Neutrophils; Pseudomonas Infections; Pseudomonas aeruginosa; Quorum Sensing; Sputum; Virulence
PY - 2007
Y1 - 2007
N2 - Quorum sensing (QS) denotes a density-dependent mode of inter-bacterial communication based on signal transmitter molecules. Active QS is present during chronic infections with the opportunistic pathogen Pseudomonas aeruginosa in immunocompromised patients. The authors have previously demonstrated a QS-regulated tolerance of biofilm bacteria to the antimicrobial properties of polymorphonuclear leukocytes (PMNs). The precise QS-regulated effect on the PMNs is, however, unknown. Incubation of human PMNs with supernatants from dense P. aeruginosa cultures showed that the QS-competent P. aeruginosa induced rapid necrosis of the PMNs. This mechanism was also observed in mouse lungs infected with P. aeruginosa, and in sputum obtained from P.-aeruginosa-infected patients with cystic fibrosis. Evidence is presented that the necrotic effect was caused by rhamnolipids, production of which is QS controlled. The results demonstrate the potential of the QS system to facilitate infections with P. aeruginosa by disabling the PMNs, which are a major first line of defence of the host. Furthermore, the study emphasizes the inhibition of QS as a target for the treatment of infections with P. aeruginosa.
AB - Quorum sensing (QS) denotes a density-dependent mode of inter-bacterial communication based on signal transmitter molecules. Active QS is present during chronic infections with the opportunistic pathogen Pseudomonas aeruginosa in immunocompromised patients. The authors have previously demonstrated a QS-regulated tolerance of biofilm bacteria to the antimicrobial properties of polymorphonuclear leukocytes (PMNs). The precise QS-regulated effect on the PMNs is, however, unknown. Incubation of human PMNs with supernatants from dense P. aeruginosa cultures showed that the QS-competent P. aeruginosa induced rapid necrosis of the PMNs. This mechanism was also observed in mouse lungs infected with P. aeruginosa, and in sputum obtained from P.-aeruginosa-infected patients with cystic fibrosis. Evidence is presented that the necrotic effect was caused by rhamnolipids, production of which is QS controlled. The results demonstrate the potential of the QS system to facilitate infections with P. aeruginosa by disabling the PMNs, which are a major first line of defence of the host. Furthermore, the study emphasizes the inhibition of QS as a target for the treatment of infections with P. aeruginosa.
U2 - 10.1099/mic.0.2006/003863-0
DO - 10.1099/mic.0.2006/003863-0
M3 - Journal article
C2 - 17464047
VL - 153
SP - 1329
EP - 1338
JO - Microbiology
JF - Microbiology
SN - 1350-0872
IS - Pt 5
ER -
ID: 10613419