Bacterial persistence increases as environmental fitness decreases

Seok Hoon Hong, Xiaoxue Wang, Hazel F. O'Connor, Michael J. Benedik, Thomas K. Wood

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

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 12000-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.

Original languageEnglish (US)
Pages (from-to)509-522
Number of pages14
JournalMicrobial Biotechnology
Volume5
Issue number4
DOIs
StatePublished - Jul 1 2012

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biochemistry
  • Applied Microbiology and Biotechnology

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