Regulation of phenotypic variability by a threshold-based mechanism underlies bacterial persistence
Open Access
- 28 June 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (28), 12541-12546
- https://doi.org/10.1073/pnas.1004333107
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.This publication has 44 references indexed in Scilit:
- Growth Rate-Dependent Global Effects on Gene Expression in BacteriaCell, 2009
- MqsR, a Crucial Regulator for Quorum Sensing and Biofilm Formation, Is a GCU-specific mRNA Interferase in Escherichia coliOnline Journal of Public Health Informatics, 2009
- The Chromosomal Toxin Gene yafQ Is a Determinant of Multidrug Tolerance for Escherichia coli Growing in a BiofilmAntimicrobial Agents and Chemotherapy, 2009
- Molecular Mechanisms of HipA-Mediated Multidrug Tolerance and Its Neutralization by HipBScience, 2009
- Drug interactions modulate the potential for evolution of resistanceProceedings of the National Academy of Sciences of the United States of America, 2008
- Single-cell protein induction dynamics reveals a period of vulnerability to antibiotics in persister bacteriaProceedings of the National Academy of Sciences of the United States of America, 2008
- Stochasticity and Cell FateScience, 2008
- Ectopic Overexpression of Wild-Type and Mutant hipA Genes in Escherichia coli : Effects on Macromolecular Synthesis and Persister FormationJournal of Bacteriology, 2006
- Stochasticity in gene expression: from theories to phenotypesNature Reviews Genetics, 2005
- Prokaryotic toxin–antitoxin stress response lociNature Reviews Microbiology, 2005