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Journal articles
Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria.
Dao Nguyen
1, *
Amruta Joshi-Datar
2
Francois Lepine
3
Elizabeth Bauerle
2
Oyebode Olakanmi
4
Karlyn Beer
2
Geoffrey Mckay
1
Richard Siehnel
2
James Schafhauser
1
Yun Wang
5
Bradley E Britigan
4, 6
Pradeep K Singh
2
Dao Nguyen 1
Correspondent author
Amruta Joshi-Datar 2
Author
Francois Lepine 3
Author
Elizabeth Bauerle 2
Author
James Schafhauser 1
Author
Yun Wang 5
Author
Bradley E Britigan 4, 6
Author
Pradeep K Singh 2
Author
1
Departments of Medicine, Microbiology and Immunology (Montreal, Quebec - Canada)
- McGill University = Université McGill [Montréal, Canada] (845, rue Sherbrooke O. Montréal (Québec) Canada H3A 0G4 - Canada)
2
Departments of Medicine and Microbiology (Seattle, WA - United States)
- University of Washington [Seattle] (Seattle, Washington 98105 - United States)
- School of Medicine (United States)
3
INRS-IAF - Institut Armand Frappier (531 boul. des Prairies Laval (Québec) H7V 1B7 - Canada)
- INRS - Institut National de la Recherche Scientifique [Québec] (490 rue de la Couronne, Québec, QC G1K 9A9 - Canada)
- RIIP - Réseau International des Instituts Pasteur (25, rue du Dr Roux 75724 Paris Cedex 15 - France)
4
Department of Internal Medicine (Cincinnati, OH - United States)
- Medical Sciences Building (France)
- UC - University of Cincinnati (2600 Clifton Ave., Cincinnati OH, Ohio 45221 - United States)
5
Department of Civil and Environmental Engineering [Evanston] (Technological Institute 2145 Sheridan Road, A236 Evanston, IL 60208 - United States)
- Northwestern University [Evanston] (633 Clark Street, Evanston, IL 60208 Evanston - United States)
6
Veterans Administration (Cincinnati, OH - United States)
- Cincinnati Children's Hospital Medical Center (3333 Burnet Avenue, Cincinnati, Ohio, OH 45229-3026 - United States)
Abstract : Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.
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Journal articles
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https://hal-riip.archives-ouvertes.fr/pasteur-00722468
Contributor : Nancy Laflamme Connect in order to contact the contributor
Submitted on : Wednesday, August 1, 2012 - 9:50:05 PM
Last modification on : Tuesday, October 19, 2021 - 11:56:24 PM
Contributor : Nancy Laflamme Connect in order to contact the contributor
Submitted on : Wednesday, August 1, 2012 - 9:50:05 PM
Last modification on : Tuesday, October 19, 2021 - 11:56:24 PM
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Identifiers
- HAL Id : pasteur-00722468, version 1
- DOI : 10.1126/science.1211037
- PUBMED : 22096200
Citation
Dao Nguyen, Amruta Joshi-Datar, Francois Lepine, Elizabeth Bauerle, Oyebode Olakanmi, et al.. Active starvation responses mediate antibiotic tolerance in biofilms and nutrient-limited bacteria.. Science, American Association for the Advancement of Science, 2011, 334 (6058), pp.982-6. ⟨10.1126/science.1211037⟩. ⟨pasteur-00722468⟩
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