Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Rotem E,Loinger A,Ronin I,Levin-Reisman I,Gabay C,Shoresh N,Biham O,Balaban NQdoi
10.1073/pnas.1004333107subject
Has Abstractpub_date
2010-07-13 00:00:00pages
12541-6issue
28eissn
0027-8424issn
1091-6490pii
1004333107journal_volume
107pub_type
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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