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Bacterial persistence increases as environmental fitness decreases
Article first published online: 6 JAN 2012
© 2012 The Authors. Microbial Biotechnology © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd
Volume 5, Issue 4, pages 509–522, July 2012
How to Cite
Hong, S. H., Wang, X., O'Connor, H. F., Benedik, M. J. and Wood, T. K. (2012), Bacterial persistence increases as environmental fitness decreases. Microbial Biotechnology, 5: 509–522. doi: 10.1111/j.1751-7915.2011.00327.x
- Issue published online: 7 JUN 2012
- Article first published online: 6 JAN 2012
- Received 6 November, 2011; accepted 7 December, 2011.
Since persister cells cause chronic infections and since Escherichia coli toxin MqsR increases persisters, we used protein engineering to increase the toxicity of MqsR to gain insights into persister cell formation. Through two amino acid replacements that increased the stability of MqsR, toxicity and persistence were increased. A whole-transcriptome study revealed that the MqsR variant increased persistence by repressing genes for acid resistance, multidrug resistance and osmotic resistance. Corroborating these microarray results, deletion of rpoS, as well as the genes that the master stress response regulator RpoS controls, increased persister formation dramatically to the extent that nearly the whole population became persistent. Furthermore, wild-type cells stressed by prior treatment to acid or hydrogen peroxide increased persistence 12 000-fold. Whole-transcriptome analyses of persister cells generated by two different methods (wild-type cells pretreated with hydrogen peroxide and the rpoS deletion) corroborated the importance of suppressing RpoS in persister cell formation. Therefore, the more toxic MqsR increases persistence by decreasing the ability of the cell to respond to antibiotic stress through its RpoS-based regulation of acid resistance, multidrug resistance and osmotic resistance systems.