Document Detail


Dynamic persistence of antibiotic-stressed mycobacteria.
MedLine Citation:
PMID:  23288538     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Exposure of an isogenic bacterial population to a cidal antibiotic typically fails to eliminate a small fraction of refractory cells. Historically, fractional killing has been attributed to infrequently dividing or nondividing "persisters." Using microfluidic cultures and time-lapse microscopy, we found that Mycobacterium smegmatis persists by dividing in the presence of the drug isoniazid (INH). Although persistence in these studies was characterized by stable numbers of cells, this apparent stability was actually a dynamic state of balanced division and death. Single cells expressed catalase-peroxidase (KatG), which activates INH, in stochastic pulses that were negatively correlated with cell survival. These behaviors may reflect epigenetic effects, because KatG pulsing and death were correlated between sibling cells. Selection of lineages characterized by infrequent KatG pulsing could allow nonresponsive adaptation during prolonged drug exposure.
Authors:
Yuichi Wakamoto; Neeraj Dhar; Remy Chait; Katrin Schneider; François Signorino-Gelo; Stanislas Leibler; John D McKinney
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  339     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-04     Completed Date:  2013-01-15     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-5     Citation Subset:  IM    
Affiliation:
School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015 Lausanne, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Antitubercular Agents / pharmacology*
Catalase / biosynthesis*,  genetics
Epigenesis, Genetic
Gene Expression Regulation, Bacterial
Isoniazid / pharmacology*
Mycobacterium smegmatis / drug effects*,  enzymology*,  genetics
Stress, Physiological*
Grant Support
ID/Acronym/Agency:
HL088906/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antitubercular Agents; 54-85-3/Isoniazid; EC 1.11.1.6/Catalase
Comments/Corrections
Comment In:
Nat Rev Microbiol. 2013 Mar;11(3):148   [PMID:  23334264 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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