The genome of Streptococcus pneumoniae is organized in topology-reacting gene clusters

The transcriptional response of Streptococcus pneumoniae was examined after exposure to the GyrB-inhibitor novobiocin. Topoisomer distributions of an internal plasmid confirmed DNA relaxation and recovery of the native level of supercoiling at low novobiocin concentrations. This was due to the up-regulation of DNA gyrase and the down-regulation of topoisomerases I and IV. In addition, >13% of the genome exhibited relaxation-dependent transcription. The majority of the responsive genes (>68%) fell into 15 physical clusters (14.6-85.6 kb) that underwent coordinated regulation, independently of operon organization. These genomic clusters correlated with AT content and codon composition, showing the chromosome to be organized into topology-reacting gene clusters that respond to DNA supercoiling. In particular, down-regulated clusters were flanked by 11-40 kb AT-rich zones that might have a putative structural function. This is the first case where genes responding to changes in the level of supercoiling in a coordinated manner were found organized as functional clusters. Such an organization revealed DNA supercoiling as a general feature that controls gene expression superimposed on other kinds of more specific regulatory mechanisms.Funding for open access charge: Plan Nacional de I + D + I of Ministerio de Ciencia e Innovación (BIO2008-02154); Comunidad de Madrid to AG de la Campa (COMBACT-S-BIO-0260/2006); from Plan Nacional de I + D + I of Ministerio de Ciencia e Innovación (BFU2008-00408/BMC to J.B.S.) in part; Ciber Enfermedades Respiratorias is an initiative from Instituto de Salud Carlos III. AG de la Campa is an Investigador Científico from de CSIC. Juan de la Cierva contract provided by Spanish Ministerio de Educación y Cultura (to A.J.M.G.).S