An increase in negative supercoiling in bacteria reveals topology-reacting gene clusters and a homeostatic response mediated by the DNA topoisomerase I gene

Ferrandiz-Avellano, Maria-JoseMartin-Galiano, Antonio JavierArnanz, CristinaCamacho-Soguero, IsabelTirado-Velez, JMde la Campa, Adela G2020-04-082020-04-082016Nucleic Acids Res. 2016 Sep 6;44(15):7292-303.0305-1048http://hdl.handle.net/20.500.12105/9487We studied the transcriptional response to an increase in DNA supercoiling in Streptococcus pneumoniae by using seconeolitsine, a new topoisomerase I inhibitor. A homeostatic response allowing recovery of supercoiling was observed in cells treated with subinhibitory seconeolitsine concentrations. Supercoiling increases of 40.7% (6 μM) and 72.9% (8 μM) were lowered to 8.5% and 44.1%, respectively. Likewise, drug removal facilitated the recovery of cell viability and DNA-supercoiling. Transcription of topoisomerase I depended on the supercoiling level. Also specific binding of topoisomerase I to the gyrase A gene promoter was detected by chromatin-immunoprecipitation. The transcriptomic response to 8 μM seconeolitsine had two stages. An early stage, associated to an increase in supercoiling, affected 10% of the genome. A late stage, manifested by supercoiling recovery, affected 2% of the genome. Nearly 25% of the early responsive genes formed 12 clusters with a coordinated transcription. Clusters were 6.7-31.4 kb in length and included 9-22 responsive genes. These clusters partially overlapped with those observed under DNA relaxation, suggesting that bacteria manage supercoiling stress using pathways with common components. This is the first report of a coordinated global transcriptomic response that is triggered by an increase in DNA supercoiling in bacteria.engVoRhttps://creativecommons.org/licenses/by-nc/4.0/BenzodioxolesDNADNA Topoisomerases, Type IDNA, BacterialDNA, SuperhelicalGene Expression Regulation, BacterialGenes, BacterialHomeostasisMicrobial ViabilityPhenanthrenesStreptococcus pneumoniaeTranscription, GeneticTranscriptomeMultigene FamilyAn increase in negative supercoiling in bacteria reveals topology-reacting gene clusters and a homeostatic response mediated by the DNA topoisomerase I geneAttribution-NonCommercial 4.0 International2737877844157292-30310.1093/nar/gkw6021362-4962Nucleic acids researchopen access