Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa

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

SN - 1350-0872

VL - 153

SP - 1329

EP - 1338

JO - Microbiology

JF - Microbiology

IS - Pt 5

ER -