title: Horizontally acquired AT-rich genes in Escherichia coli cause toxicity by sequestering RNA polymerase.
abstract: Horizontal gene transfer permits rapid dissemination of genetic elements between individuals in bacterial populations. Transmitted DNA sequences may encode favourable traits. However, if the acquired DNA has an atypical base composition, it can reduce host fitness. Consequently, bacteria have evolved strategies to minimize the harmful effects of foreign genes. Most notably, xenogeneic silencing proteins bind incoming DNA that has a higher AT content than the host genome. An enduring question has been why such sequences are deleterious. Here, we showed that the toxicity of AT-rich DNA in Escherichia coli frequently results from constitutive transcription initiation within the coding regions of genes. Left unchecked, this causes titration of RNA polymerase and a global downshift in host gene expression. Accordingly, a mutation in RNA polymerase that diminished the impact of AT-rich DNA on host fitness reduced transcription from constitutive, but not activator-dependent, promoters.
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Lamberte
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Baniulyte
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Shivani S
authors.initials: SS
authors.lastname: Singh
authors.affiliation: New York State Department of Health, Wadsworth Center, Albany, New York 12208, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Stringer
authors.affiliation: New York State Department of Health, Wadsworth Center, Albany, New York 12208, USA.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bonocora
authors.affiliation: Biological Physics Research Group, Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK.
authors.forename: Mathew
authors.initials: M
authors.lastname: Stracy
authors.affiliation: Biological Physics Research Group, Clarendon Laboratory, Department of Physics, University of Oxford, Oxford OX1 3PU, UK.
authors.forename: Achillefs N
authors.initials: AN
authors.lastname: Kapanidis
authors.affiliation: New York State Department of Health, Wadsworth Center, Albany, New York 12208, USA.|Department of Biomedical Sciences, School of Public Health, University at Albany, State University of New York, Albany, New York 12201, USA.
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Wade
authors.affiliation: Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: David C
authors.initials: DC
authors.lastname: Grainger
mesh_terms: D020856:AT Rich Sequence / Q000235:genetics*; D001482:Base Composition; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D012321:DNA-Directed RNA Polymerases / Q000235:genetics* / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D036781:Fimbriae Proteins / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D020868:Gene Silencing; D022761:Gene Transfer, Horizontal; D005798:Genes, Bacterial; D056084:Genetic Fitness; D016678:Genome; D009154:Mutation; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D004269:DNA, Bacterial; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C529458:FimG protein, E coli; D036781:Fimbriae Proteins; D012321:DNA-Directed RNA Polymerases