Publication Date:
2013-01-05
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wakamoto, Yuichi -- Dhar, Neeraj -- Chait, Remy -- Schneider, Katrin -- Signorino-Gelo, Francois -- Leibler, Stanislas -- McKinney, John D -- HL088906/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2013 Jan 4;339(6115):91-5. doi: 10.1126/science.1229858.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Life Sciences, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015 Lausanne, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23288538" target="_blank"〉PubMed〈/a〉
Keywords:
Antitubercular Agents/*pharmacology
;
Catalase/*biosynthesis/genetics
;
Epigenesis, Genetic
;
Gene Expression Regulation, Bacterial
;
Isoniazid/*pharmacology
;
Mycobacterium smegmatis/*drug effects/*enzymology/genetics
;
*Stress, Physiological
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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