Publication Date:
2011-11-19
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046891/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nguyen, Dao -- Joshi-Datar, Amruta -- Lepine, Francois -- Bauerle, Elizabeth -- Olakanmi, Oyebode -- Beer, Karlyn -- McKay, Geoffrey -- Siehnel, Richard -- Schafhauser, James -- Wang, Yun -- Britigan, Bradley E -- Singh, Pradeep K -- K24 HL102246/HL/NHLBI NIH HHS/ -- R01 AI101307/AI/NIAID NIH HHS/ -- R56 AI091714/AI/NIAID NIH HHS/ -- Canadian Institutes of Health Research/Canada -- New York, N.Y. -- Science. 2011 Nov 18;334(6058):982-6. doi: 10.1126/science.1211037.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Medicine, Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. dao.nguyen@mcgill.ca〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22096200" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Anti-Bacterial Agents/*pharmacology/therapeutic use
;
Biofilms/*drug effects/growth & development
;
Catalase/metabolism
;
Drug Resistance, Bacterial
;
Drug Tolerance
;
Escherichia coli/drug effects/genetics/growth & development/physiology
;
Female
;
Hydroxyl Radical/metabolism
;
Hydroxyquinolines/metabolism
;
Mice
;
Mice, Inbred C57BL
;
Mutation
;
Ofloxacin/pharmacology/therapeutic use
;
Oxidative Stress
;
Pseudomonas Infections/drug therapy/*microbiology
;
Pseudomonas aeruginosa/*drug effects/genetics/growth & development/*physiology
;
Serine/analogs & derivatives/pharmacology
;
Superoxide Dismutase/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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