Horizontally acquired AT-rich genes in Escherichia coli cause toxicity by sequestering RNA polymerase

• Published in: Nature microbiology Vol. 2; no. 3; p. 16249
• Main Authors: Lamberte, Lisa E., Baniulyte, Gabriele, Singh, Shivani S., Stringer, Anne M., Bonocora, Richard P., Stracy, Mathew, Kapanidis, Achillefs N., Wade, Joseph T., Grainger, David C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.01.2017; Nature Publishing Group
• Subjects: 631/326/325; 631/326/41/1969; 631/337/572/2102; AT Rich Sequence - genetics; Base Composition; Biomedical and Life Sciences; Deoxyribonucleic acid; DNA; DNA, Bacterial - chemistry; DNA, Bacterial - genetics; DNA, Bacterial - metabolism; DNA-Binding Proteins - metabolism; DNA-directed RNA polymerase; DNA-Directed RNA Polymerases - genetics; DNA-Directed RNA Polymerases - metabolism; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli Proteins - metabolism; Fimbriae Proteins - metabolism; Gene expression; Gene Expression Regulation, Bacterial; Gene Silencing; Gene transfer; Gene Transfer, Horizontal; Genes, Bacterial; Genetic Fitness; Genome; Genomes; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Mutation; Nucleotide sequence; Parasitology; Promoter Regions, Genetic; Reproductive fitness; RNA polymerase; Titration; Toxicity; Transcription initiation; Transcription, Genetic; Virology
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/nmicrobiol.2016.249

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. Horizontally acquired AT-rich sequences contain cryptic promoters that sequester RNA polymerase and mediate toxicity in Escherichia coli .