Suppression of the Escherichia coli dnaA46 mutation by changes in the activities of the pyruvate-acetate node links DNA replication regulation to central carbon metabolism.

Joanna Tymecka-Mulik,Lidia Boss,João F Matias Rodrigues,Anna Wosinski,Grzegorz Węgrzyn,Lidia Gaffke,Grzegorz M Cech,Monika Maciąg-Dorszyńska,Agnieszka Szalewska-Pałasz,Monika Glinkowska,Sergey Korolev

doi:10.1371/journal.pone.0176050

Joanna Tymecka-Mulik, Lidia Boss + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0176050

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Journal: PloS one	Publication Date: Apr 27, 2017
Citations: 20	License type: CC BY 4.0

Affiliation: University of Gdańsk, University of Zurich

Abstract

To ensure faithful transmission of genetic material to progeny cells, DNA replication is tightly regulated, mainly at the initiation step. Escherichia coli cells regulate the frequency of initiation according to growth conditions. Results of the classical, as well as the latest studies, suggest that the DNA replication in E. coli starts at a predefined, constant cell volume per chromosome but the mechanisms coordinating DNA replication with cell growth are still not fully understood. Results of recent investigations have revealed a role of metabolic pathway proteins in the control of cell division and a direct link between metabolism and DNA replication has also been suggested both in Bacillus subtilis and E. coli cells. In this work we show that defects in the acetate overflow pathway suppress the temperature-sensitivity of a defective replication initiator–DnaA under acetogenic growth conditions. Transcriptomic and metabolic analyses imply that this suppression is correlated with pyruvate accumulation, resulting from alterations in the pyruvate dehydrogenase (PDH) activity. Consequently, deletion of genes encoding the pyruvate dehydrogenase subunits likewise resulted in suppression of the thermal-sensitive growth of the dnaA46 strain. We propose that the suppressor effect may be directly related to the PDH complex activity, providing a link between an enzyme of the central carbon metabolism and DNA replication.

Highlights

In their natural environment bacteria often come across drastic variations in growth conditions as well as competition with other species
This result further confirmed that the suppression, observed in the LB medium, is not a simple consequence of the slower growth rate of the Connecting metabolism to DNA replication in Escherichia coli mutants, since if this was the case, the observed suppression should be strongest in media supporting slow growth, i.e. in glycerol
In this work we have shown that the suppression of dnaA46 phenotypes by the absence of a part, or the whole acetate overflow pathway, depends on the growth conditions and occurs during fast growth in an acetogenic medium but not when glycerol is used as a sole carbon source (Fig 1)

Summary

Introduction

In their natural environment bacteria often come across drastic variations in growth conditions as well as competition with other species. Bacterial cells need to constantly coordinate the chromosomal DNA replication and cell division with cell growth, to ensure faithful transmission of the genetic material to progeny cells while. Connecting metabolism to DNA replication in Escherichia coli. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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