Transcriptomics

Dataset Information

3

Plasticity of transcriptional regulation under antibiotic stress


ABSTRACT: Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here we demonstrate that inactivation of a central regulator of iron homeostasis (fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated a substantial reorganization of the Fur regulon in response to antibiotic treatment. We hypothesized that the impact of Fur on evolvability under antibiotic pressure is due to the elevated intracellular concentration of free iron and the consequent enhancement of oxidative damage-induced mutagenesis. In agreement with expectations, over-expression of iron storage proteins, inhibition of iron transport, or anaerobic conditions drastically suppressed the evolution of resistance, while inhibition of the SOS response-mediated mutagenesis had no such effect in fur deficient population. In sum, our work revealed the central role of iron metabolism in de novo evolution of antibiotic resistance, a pattern that could influence the development of novel antimicrobial strategies. We used microarrays to identify genotype specific transcriptional changes under severe DNA damaging conditions (antibiotic ciprofloxacin). We treated Escherichia coli cells with a highly toxic level of ciprofloxacin (gyrase inhibitor) for RNA extraction and hybridization on Affymetrix microarrays. We planned to find genotype specific transcriptional responses using WT control (BW25113) and fur-knockout mutant (selected from the KEIO collection) strains during antibiotic treatments. For each treatment type we used two biological replicates.

ORGANISM(S): Escherichia coli K-12  

SUBMITTER: Balazs Bogos   Bálint Csörgő  Csaba Pál  Balázs Bogos  Ferenc Pál  Orsolya Méhi  Balázs Papp   Ákos Nyerges 

PROVIDER: E-GEOD-55662 | ArrayExpress | 2014-09-11

SECONDARY ACCESSION(S): GSE55662PRJNA240315

REPOSITORIES: GEO, ArrayExpress

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Publications

Perturbation of iron homeostasis promotes the evolution of antibiotic resistance.

Méhi Orsolya O   Bogos Balázs B   Csörgő Bálint B   Pál Ferenc F   Nyerges Akos A   Papp Balázs B   Pál Csaba C  

Molecular biology and evolution 20140724 10


Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here, we demonstrate that inactivation of a central transcriptional regulator of iron homeostasis (Fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated that the set of genes regulated by Fur changes substantia  ...[more]

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