title: Chromosomal position shift of a regulatory gene alters the bacterial phenotype.
abstract: Recent studies strongly suggest that in bacterial cells the order of genes along the chromosomal origin-to-terminus axis is determinative for regulation of the growth phase-dependent gene expression. The prediction from this observation is that positional displacement of pleiotropic genes will affect the genetic regulation and hence, the cellular phenotype. To test this prediction we inserted the origin-proximal dusB-fis operon encoding the global regulator FIS in the vicinity of replication terminus on both arms of the Escherichia coli chromosome. We found that the lower fis gene dosage in the strains with terminus-proximal dusB-fis operons was compensated by increased fis expression such that the intracellular concentration of FIS was homeostatically adjusted. Nevertheless, despite unchanged FIS levels the positional displacement of dusB-fis impaired the competitive growth fitness of cells and altered the state of the overarching network regulating DNA topology, as well as the cellular response to environmental stress, hazardous substances and antibiotics. Our finding that the chromosomal repositioning of a regulatory gene can determine the cellular phenotype unveils an important yet unexplored facet of the genetic control mechanisms and paves the way for novel approaches to manipulate bacterial physiology.
authors.affiliation: Jacobs University Bremen, School of Engineering and Science, Bremen, 28758, Germany.
authors.forename: Veneta
authors.initials: V
authors.lastname: Gerganova
authors.affiliation: Institut für Hygiene, Universitätsklinikum Münster, Münster, 48149, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Berger
authors.affiliation: Jacobs University Bremen, School of Engineering and Science, Bremen, 28758, Germany.
authors.forename: Elisabed
authors.initials: E
authors.lastname: Zaldastanishvili
authors.affiliation: Philipps-Universität Marburg, LOEWE-Zentrum für Synthetische Mikrobiologie, Department of Chromosome Biology, Marburg, 35032, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sobetzko
authors.affiliation: SANOFI/ TSU Infectious Diseases, Toulouse, 31036, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Lafon
authors.affiliation: SANOFI/ TSU Infectious Diseases, Toulouse, 31036, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Mourez
authors.affiliation: MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Travers
authors.affiliation: Jacobs University Bremen, School of Engineering and Science, Bremen, 28758, Germany g.muskhelishvili@jacobs-university.de.
authors.forename: Georgi
authors.initials: G
authors.lastname: Muskhelishvili
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D045584:Chromosome Positioning; D002876:Chromosomes, Bacterial; D004278:DNA, Superhelical / Q000032:analysis; D048168:Escherichia coli K12 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000096:biosynthesis / Q000235:genetics*; D035021:Factor For Inversion Stimulation Protein / Q000096:biosynthesis / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D005809:Genes, Regulator; D009876:Operon; D018384:Oxidative Stress; D010641:Phenotype
chemical_list: D000900:Anti-Bacterial Agents; D004278:DNA, Superhelical; D029968:Escherichia coli Proteins; D035021:Factor For Inversion Stimulation Protein; C501034:Fis protein, E coli