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Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo

Gilles Brackman UGent, Paul Cos, Louis Maes, Hans Nelis UGent and Tom Coenye UGent (2011) ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 55(6). p.2655-2661
abstract
Although the exact role of quorum sensing (QS) in various stages of biofilm formation, maturation, and dispersal and in biofilm resistance is not entirely clear, the use of QS inhibitors (QSI) has been proposed as a potential antibiofilm strategy. We have investigated whether QSI enhance the susceptibility of bacterial biofilms to treatment with conventional antimicrobial agents. The QSI used in our study target the acylhomoserine lactone-based QS system present in Pseudomonas aeruginosa and Burkholderia cepacia complex organisms (baicalin hydrate, cinnamaldehyde) or the peptide-based system present in Staphylococcus aureus (hamamelitannin). The effect of tobramycin (P. aeruginosa, B. cepacia complex) and clindamycin or vancomycin (S. aureus), alone or in combination with QSI, was evaluated in various in vitro and in vivo biofilm model systems, including two invertebrate models and one mouse pulmonary infection model. In vitro the combined use of an antibiotic and a QSI generally resulted in increased killing compared to killing by an antibiotic alone, although reductions were strain and model dependent. A significantly higher fraction of infected Galleria mellonella larvae and Caenorhabditis elegans survived infection following combined treatment, compared to treatment with an antibiotic alone. Finally, the combined use of tobramycin and baicalin hydrate reduced the microbial load in the lungs of BALB/ c mice infected with Burkholderia cenocepacia more than tobramycin treatment alone. Our data suggest that QSI may increase the success of antibiotic treatment by increasing the susceptibility of bacterial biofilms and/ or by increasing host survival following infection.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
CAENORHABDITIS-ELEGANS, BURKHOLDERIA-CEPACIA COMPLEX, PSEUDOMONAS-AERUGINOSA, CYSTIC-FIBROSIS, MODEL HOST, INFECTION, IDENTIFICATION, COMMUNICATION, PATHOGENESIS, ENVIRONMENT
journal title
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Antimicrob. Agents Chemother.
volume
55
issue
6
pages
2655 - 2661
Web of Science type
Article
Web of Science id
000290713400024
JCR category
PHARMACOLOGY & PHARMACY
JCR impact factor
4.841 (2011)
JCR rank
24/259 (2011)
JCR quartile
1 (2011)
ISSN
0066-4804
DOI
10.1128/AAC.00045-11
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1891511
handle
http://hdl.handle.net/1854/LU-1891511
date created
2011-08-22 15:21:49
date last changed
2011-08-23 11:16:24
@article{1891511,
  abstract     = {Although the exact role of quorum sensing (QS) in various stages of biofilm formation, maturation, and dispersal and in biofilm resistance is not entirely clear, the use of QS inhibitors (QSI) has been proposed as a potential antibiofilm strategy. We have investigated whether QSI enhance the susceptibility of bacterial biofilms to treatment with conventional antimicrobial agents. The QSI used in our study target the acylhomoserine lactone-based QS system present in Pseudomonas aeruginosa and Burkholderia cepacia complex organisms (baicalin hydrate, cinnamaldehyde) or the peptide-based system present in Staphylococcus aureus (hamamelitannin). The effect of tobramycin (P. aeruginosa, B. cepacia complex) and clindamycin or vancomycin (S. aureus), alone or in combination with QSI, was evaluated in various in vitro and in vivo biofilm model systems, including two invertebrate models and one mouse pulmonary infection model. In vitro the combined use of an antibiotic and a QSI generally resulted in increased killing compared to killing by an antibiotic alone, although reductions were strain and model dependent. A significantly higher fraction of infected Galleria mellonella larvae and Caenorhabditis elegans survived infection following combined treatment, compared to treatment with an antibiotic alone. Finally, the combined use of tobramycin and baicalin hydrate reduced the microbial load in the lungs of BALB/ c mice infected with Burkholderia cenocepacia more than tobramycin treatment alone. Our data suggest that QSI may increase the success of antibiotic treatment by increasing the susceptibility of bacterial biofilms and/ or by increasing host survival following infection.},
  author       = {Brackman, Gilles and Cos, Paul and Maes, Louis and Nelis, Hans and Coenye, Tom},
  issn         = {0066-4804},
  journal      = {ANTIMICROBIAL AGENTS AND CHEMOTHERAPY},
  keyword      = {CAENORHABDITIS-ELEGANS,BURKHOLDERIA-CEPACIA COMPLEX,PSEUDOMONAS-AERUGINOSA,CYSTIC-FIBROSIS,MODEL HOST,INFECTION,IDENTIFICATION,COMMUNICATION,PATHOGENESIS,ENVIRONMENT},
  language     = {eng},
  number       = {6},
  pages        = {2655--2661},
  title        = {Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo},
  url          = {http://dx.doi.org/10.1128/AAC.00045-11},
  volume       = {55},
  year         = {2011},
}

Chicago
Brackman, Gilles, Paul Cos, Louis Maes, Hans Nelis, and Tom Coenye. 2011. “Quorum Sensing Inhibitors Increase the Susceptibility of Bacterial Biofilms to Antibiotics in Vitro and in Vivo.” Antimicrobial Agents and Chemotherapy 55 (6): 2655–2661.
APA
Brackman, G., Cos, P., Maes, L., Nelis, H., & Coenye, T. (2011). Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55(6), 2655–2661.
Vancouver
1.
Brackman G, Cos P, Maes L, Nelis H, Coenye T. Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2011;55(6):2655–61.
MLA
Brackman, Gilles, Paul Cos, Louis Maes, et al. “Quorum Sensing Inhibitors Increase the Susceptibility of Bacterial Biofilms to Antibiotics in Vitro and in Vivo.” ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 55.6 (2011): 2655–2661. Print.