quorum sensing and virulence of pseudomonas aeruginosa during lung infection of cystic fibrosis patients群体感应和毒性铜绿假单胞菌在囊性纤维化患者的肺部感染.pdfVIP

Quorum Sensing and Virulence of Pseudomonas aeruginosa during Lung Infection of Cystic Fibrosis Patients 1 2 1 3 Thomas Bjarnsholt , Peter Østrup Jensen , Tim Holm Jakobsen , Richard Phipps , Anne Kirstine 1 1 1 1 1,2 1 Nielsen , Morten Theil Rybtke , Tim Tolker-Nielsen , Michael Givskov , Niels Høiby , Oana Ciofu *, the Scandinavian Cystic Fibrosis Study Consortium 1 Institute for International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark, 2 Department of Clinical Microbiology, University Hospital, Rigshospitalet, Copenhagen, Denmark, 3 BioSys, Technical University of Denmark, Lyngby, Denmark Abstract Pseudomonas aeruginosa is the predominant microorganism in chronic lung infection of cystic fibrosis patients. The chronic lung infection is preceded by intermittent colonization. When the chronic infection becomes established, it is well accepted that the isolated strains differ phenotypically from the intermittent strains. Dominating changes are the switch to mucoidity (alginate overproduction) and loss of epigenetic regulation of virulence such as the Quorum Sensing (QS). To elucidate the dynamics of P. aeruginosa QS systems during long term infection of the CF lung, we have investigated 238 isolates obtained from 152 CF patients at different stages of infection ranging from intermittent to late chronic. Isolates were characterized with regard to QS signal molecules, alginate, rhamnolipid and elastase production and mutant frequency. The genetic basis for change in QS regulation were investigated and identified by sequence analysis of lasR, rhlR, lasI and rhl