Regulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence.

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.

authors

Rotem E,Loinger A,Ronin I,Levin-Reisman I,Gabay C,Shoresh N,Biham O,Balaban NQ

doi

10.1073/pnas.1004333107

subject

Has Abstract

pub_date

2010-07-13 00:00:00

pages

12541-6

issue

28

eissn

0027-8424

issn

1091-6490

pii

1004333107

journal_volume

107

pub_type

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