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The genome-scale interplay amongst xenogene silencing, stress response and chromosome architecture in Escherichia coli.

ABSTRACT: The gene expression state of exponentially growing Escherichia coli cells is manifested by high expression of essential and growth-associated genes and low levels of stress-related and horizontally acquired genes. An important player in maintaining this homeostasis is the H-NS-StpA gene silencing system. A ?hns-stpA deletion mutant results in high expression of otherwise-silent horizontally acquired genes, many located in the terminus-half of the chromosome, and an indirect downregulation of many highly expressed genes. The ?hns-stpA double mutant displays slow growth. Using laboratory evolution we address the evolutionary strategies that E. coli would adopt to redress this gene expression imbalance. We show that two global gene regulatory mutations-(i) point mutations inactivating the stress-responsive sigma factor RpoS or ?38 and (ii) an amplification of ?40% of the chromosome centred around the origin of replication-converge in partially reversing the global gene expression imbalance caused by ?hns-stpA. Transcriptome data of these mutants further show a three-way link amongst the global gene regulatory networks of H-NS and ?38, as well as chromosome architecture. Increasing gene expression around the terminus of replication results in a decrease in the expression of genes around the origin and vice versa; this appears to be a persistent phenomenon observed as an association across ?300 publicly-available gene expression data sets for E. coli. These global suppressor effects are transient and rapidly give way to more specific mutations, whose roles in reversing the growth defect of H-NS mutations remain to be understood.

SUBMITTER: Srinivasan R

PROVIDER: S-EPMC4288151 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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The genome-scale interplay amongst xenogene silencing, stress response and chromosome architecture in Escherichia coli.

Srinivasan Rajalakshmi R Scolari Vittore Ferdinando VF Lagomarsino Marco Cosentino MC Seshasayee Aswin Sai Narain AS

Nucleic acids research 20141127 1

The gene expression state of exponentially growing Escherichia coli cells is manifested by high expression of essential and growth-associated genes and low levels of stress-related and horizontally acquired genes. An important player in maintaining this homeostasis is the H-NS-StpA gene silencing system. A Δhns-stpA deletion mutant results in high expression of otherwise-silent horizontally acquired genes, many located in the terminus-half of the chromosome, and an indirect downregulation of man ...[more]

PMID: 25429971

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Project description:We have previously reported that supplementation of exogenous glutathione (GSH) promotes ciprofloxacin resistance in Escherichia coli by neutralizing antibiotic-induced oxidative stress and by enhancing the efflux of antibiotic. In the present study, we used a whole-genome microarray as a tool to analyze the system-level transcriptomic changes of E. coli on exposure to GSH and/or ciprofloxacin. The microarray data revealed that GSH supplementation affects redox function, transport, acid shock, and virulence genes of E. coli. The data further highlighted the interplay of multiple underlying stress response pathways (including those associated with the genes mentioned above and DNA damage repair genes) at the core of GSH, offsetting the effect of ciprofloxacin in E. coli. The results of a large-scale validation of the transcriptomic data using reverse transcription-quantitative PCR (RT-qPCR) analysis for 40 different genes were mostly in agreement with the microarray results. The altered growth profiles of 12 different E. coli strains carrying deletions in the specific genes mentioned above with GSH and/or ciprofloxacin supplementation implicate these genes in the GSH-mediated phenotype not only at the molecular level but also at the functional level. We further associated GSH supplementation with increased acid shock survival of E. coli on the basis of our transcriptomic data. Taking the data together, it can be concluded that GSH supplementation influences the expression of genes of multiple stress response pathways apart from its effect(s) at the physiological level to counter the action of ciprofloxacin in E. coli. IMPORTANCE The emergence and spread of multidrug-resistant bacterial strains have serious medical and clinical consequences. In addition, the rate of discovery of new therapeutic antibiotics has been inadequate in last few decades. Fluoroquinolone antibiotics such as ciprofloxacin represent a precious therapeutic resource in the fight against bacterial pathogens. However, these antibiotics have been gradually losing their appeal due to the emergence and buildup of resistance to them. In this report, we shed light on the genome-level expression changes in bacteria with respect to glutathione (GSH) exposure which act as a trigger for fluoroquinolone antibiotic resistance. The knowledge about different bacterial stress response pathways under conditions of exposure to the conditions described above and potential points of cross talk between them could help us in understanding and formulating the conditions under which buildup and spread of antibiotic resistance could be minimized. Our findings are also relevant because GSH-induced genome-level expression changes have not been reported previously for E. coli.

Dataset Information

The genome-scale interplay amongst xenogene silencing, stress response and chromosome architecture in Escherichia coli.

Publications

The genome-scale interplay amongst xenogene silencing, stress response and chromosome architecture in Escherichia coli.

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