In vitro screens for quorum sensing inhibitors and in vivo confirmation of their effect

Nature Protocols

Volumn 5, Issue 2, 2010, Pages 282-293

  Bjarnsholt, Thomas ^a,b   Van Gennip, Maria ^a   Jakobsen, Tim H ^a   Christensen, Louise D ^a   Jensen, Peter Ø ^b   Givskov, Michael ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b Rigshospitalet   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; GARLIC EXTRACT; N ACYLHOMOSERINE LACTONE; PATULIN; QUORUM SENSING INHIBITOR; SILICONE; TRANSCRIPTION FACTOR LUXR; UNCLASSIFIED DRUG;

ARTICLE; BIOFILM; BIOLOGICAL ACTIVITY; COLONY FORMING UNIT; CULTURE MEDIUM; CYSTIC FIBROSIS; DOSE RESPONSE; FLOW CYTOMETRY; HUMAN; IN VITRO STUDY; IN VIVO STUDY; LUNG INFECTION; MICROARRAY ANALYSIS; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; QUANTITATIVE ASSAY; QUORUM SENSING;

ANIMALS; ANTI-BACTERIAL AGENTS; BACTERIA; BACTERIOLOGICAL TECHNIQUES; DISEASE MODELS, ANIMAL; DRUG RESISTANCE, BACTERIAL; ESCHERICHIA COLI INFECTIONS; GRAM-NEGATIVE BACTERIA; HUMANS; LUNG DISEASES; MICROSCOPY, CONFOCAL; MICROSCOPY, ELECTRON, SCANNING; MODELS, ANIMAL; QUORUM SENSING;

ANIMALIA; BACTERIA (MICROORGANISMS);

EID: 76649136943     PISSN: 17542189     EISSN: 17502799     Source Type: Journal    
DOI: 10.1038/nprot.2009.205     Document Type: Article

References (27)

1. Fuqua, W.C., Winans, S.C. & Greenberg, E.P. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J. Bacteriol. 176, 269-275 (1994).
2. Hentzer, M. et al. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J. 22, 3803-3815 (2003).
3. Bjarnsholt, T. et al. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections. Microbiology 151, 3873-3880 (2005).
4. Bjarnsholt, T. et al. Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent. Microbiology 151, 373-383 (2005).
5. Christensen, L.D. et al. Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model. Microbiology 153, 2312-2320 (2007).
6. Jensen, P.O. et al. Rapid necrotic killing of polymorphonuclear leukocytes is caused by quorum-sensing-controlled production of rhamnolipid by Pseudomonas aeruginosa. Microbiology 153, 1329-1338 (2007).
7. Costerton, J.W., Stewart, P.S. & Greenberg, E.P. Bacterial biofilms: a common cause of persistent infections. Science 284, 1318-1322 (1999).
8. Kirketerp-Moller, K. et al. Distribution, organization, and ecology of bacteria in chronic wounds. J Clin. Microbiol. 46, 2717-2722 (2008).
9. Homoe, P., Bjarnsholt, T., Wessman, M., Sorensen, H.C. & Johansen, H.K. Morphological evidence of biofilm formation in Greenlanders with chronic suppurative otitis media. Eur. Arch. Otorhinolaryngol. (2009).
10. Bjarnsholt, T., Tolker-Nielsen, T., Givskov, M., Janssen, M. & Chrsitensen, L. Detection of bacteria by FISH in culture-negative soft tissue filler lesions. Dermatol. Surg. in press. (2009).
11. Bjarnsholt, T. et al. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr. Pulmonol. 44, 547-558 (2009).
12. Neut, D., van, H., Jr., van Kooten, T.G., van der Mei, H.C. & Busscher, H.J. Detection of biomaterial-associated infections in orthopaedic joint implants. Clin. Orthop. Relat. Res. 261-268 (2003).
13. Givskov, M. et al. Eukaryotic interference with homoserine lactone-mediated prokaryotic signalling. J. Bacteriol. 178, 6618-6622 (1996).
14. Wu, H. et al. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J. Antimicrob. Chemother. 53, 1054-1061 (2004).
15. Rasmussen, T.B. et al. Identity and effects of quorum sensing inhibitors produced by Penicillum species. Microbiology 151, 1325-1340 (2005).
16. Skindersoe, M.E. et al. Quorum sensing antagonism from marine organisms. Mar. Biotechnol. (NY) 10, 56-63 (2008).
17. Rasmussen, T.B. et al. Screening for quorum sensing inhibitors using a novel genetic system-the QSI selector. J. Bacteriol. 187, 1799 - 1814 (2005).
18. Skindersoe, M.E. et al. Effects of antibiotics on quorum sensing in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52, 3648-3663 (2008).
19. Yang, L. et al. Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors. Antimicrob. Agents Chemother. 53, 2432-2443 (2009).
20. Ravn, L., Christensen, A.B., Molin, S., Givskov, M. & Gram, L. Methods for detecting acylated homoserine lactones produced by Gram-negative bacteria and their application in studies of AHL-production kinetics. J Microbiol. Methods 44, 239-251 (2001).
21. Hentzer, M. et al. Inhibition of quorum sensing in Pseudomonas aeruginosa biofilm bacteria by a halogenated furanone compound. Microbiology 148, 87-102 (2002).
22. Pedersen, S.S., Shand, G.H., Hansen, B.L. & Hansen, G.N. Induction of experimental chronic Pseudomonas aeruginosa lung infection with P. aeruginosa entrapped in alginate microspheres. APMIS 98, 203-211 (1990).
23. Wu, H. et al. Detection of N-acylhomoserine lactones in lung tissues of mice infected with Pseudomonas aeruginosa. Microbiology 146 (Pt 10): 2481-2493 (2000).
24. Buret, A., Ward, K.H., Olson, M.E. & Costerton, J.W. An in vivo model to study the pathobiology of infectious biofilms on biomaterial surfaces. J. Biomed. Mater. Res. 25, 865-874 (1991).
25. van, G.M. et al. Inactivation of the rhlA gene in Pseudomonas aeruginosa prevents rhamnolipid production, disabling the protection against polymorphonuclear leukocytes. APMIS 117, 537-546 (2009).
26. Kohler, T., van Delden, C., Curty, L.K., Hamzehpour, M.M. & Pechere, J.C. Overexpression of the MexEF-OprNmultidrug efflux system affects cell-to-cell signaling in Pseudomonas aeruginosa. J. Bacteriol. 183, 5213-5222 (2001).
27. Høiby, N. Epidemiological investigations of the respiratory tract bacteriology in patients with cystic fibrosis. Acta. Pathol. Microbiol. Scand. B Microbiol. Immunol. 82, 541-550 (1974).