Document Detail

Regulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence.
MedLine Citation:
PMID:  20616060     Owner:  NLM     Status:  MEDLINE    
In the face of antibiotics, bacterial populations avoid extinction by harboring a subpopulation of dormant cells that are largely drug insensitive. This phenomenon, termed "persistence," is a major obstacle for the treatment of a number of infectious diseases. The mechanism that generates both actively growing as well as dormant cells within a genetically identical population is unknown. We present a detailed study of the toxin-antitoxin module implicated in antibiotic persistence of Escherichia coli. We find that bacterial cells become dormant if the toxin level is higher than a threshold, and that the amount by which the threshold is exceeded determines the duration of dormancy. Fluctuations in toxin levels above and below the threshold result in coexistence of dormant and growing cells. We conclude that toxin-antitoxin modules in general represent a mixed network motif that can serve to produce a subpopulation of dormant cells and to supply a mechanism for regulating the frequency and duration of growth arrest. Toxin-antitoxin modules thus provide a natural molecular design for implementing a bet-hedging strategy.
Eitan Rotem; Adiel Loinger; Irine Ronin; Irit Levin-Reisman; Chana Gabay; Noam Shoresh; Ofer Biham; Nathalie Q Balaban
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-28
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-14     Completed Date:  2010-08-19     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12541-6     Citation Subset:  IM    
Racah Institute of Physics, Center for Nanoscience and Nanotechnology, Sudarsky Center for Computational Biology, Hebrew University, Jerusalem 91904, Israel.
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MeSH Terms
Anti-Bacterial Agents / pharmacology
Antitoxins / genetics,  pharmacology
Bacteria / genetics,  metabolism
Escherichia coli / genetics*,  growth & development,  physiology*
Glycogen Storage Disease Type IIb / genetics
Myopathy, Central Core / genetics
Optic Atrophy, Autosomal Dominant / genetics
Urea Cycle Disorders, Inborn
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antitoxins

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