Synthetic tolerance: Three noncoding small RNAs, DsrA, ArcZ and RprA, acting supra-additively against acid stress

Stefan M. Gaida, Mohab A. Al-Hinai, Dinesh C. Indurthi, Sergios A. Nicolaou, Eleftherios T. Papoutsakis

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

Synthetic acid tolerance, especially during active cell growth, is a desirable phenotype for many biotechnological applications. Natively, acid resistance in Escherichia coli is largely a stationary-phase phenotype attributable to mechanisms mostly under the control of the stationary-phase sigma factor RpoS. We show that simultaneous overexpression of noncoding small RNAs (sRNAs), DsrA, RprA and ArcZ, which are translational RpoS activators, increased acid tolerance (based on a low-pH survival assay) supra-additively up to 8500-fold during active cell growth, and provided protection against carboxylic acid and oxidative stress. Overexpression of rpoS without its regulatory 5′-UTR resulted in inferior acid tolerance. The supra-additive effect of overexpressing the three sRNAs results from the impact their expression has on RpoS-protein levels, and the beneficial perturbation of the interconnected RpoS and H-NS networks, thus leading to superior tolerance during active growth. Unlike the overexpression of proteins, overexpression of sRNAs imposes hardly any metabolic burden on cells, and constitutes a more effective strain engineering strategy.

Original languageEnglish
Pages (from-to)8726-8737
Number of pages12
JournalNucleic Acids Research
Volume41
Issue number18
DOIs
Publication statusPublished - Oct 2013

ASJC Scopus subject areas

  • Genetics

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