DNA supercoiling acts as a global and ancestral regulator of bacterial gene expression. In this review, we advocate that it plays a pivotal role in host-pathogen interactions by transducing environmental signals to the bacterial chromosome and coordinating its transcriptional response. We present available evidence that DNA supercoiling is modulated by environmental stress conditions relevant to the infection process according to ancestral mechanisms, in zoopathogens as well as phytopathogens. We review the results of transcriptomics studies obtained in widely distant bacterial species, showing that such structural transitions of the chromosome are associated to a complex transcriptional response affecting a large fraction of the genome. Mechanisms and computational models of the transcriptional regulation by DNA supercoiling are then discussed, involving both basal interactions of RNA Polymerase with promoter DNA, and more specific interactions with regulatory proteins. A final part is specifically focused on the regulation of virulence genes within pathogenicity islands of several pathogenic bacterial species.
DNA supercoiling is an essential mechanism of bacterial chromosome compaction, whose level is mainly regulated by topoisomerase I and DNA gyrase. Inhibiting either of these enzymes with antibiotics leads to global supercoiling modifications and subsequent changes in global gene expression. In previous studies, genes responding to DNA relaxation induced by gyrase inhibition were categorized as "supercoiling-sensitive". Here, we studied the opposite variation of DNA supercoiling in the phytopathogen Dickeya dadantii using the non-marketed antibiotic seconeolitsine, and obtained the first transcriptomic response of a Gram-negative bacterium to topoisomerase I inhibition. We find that the responding genes essentially differ from those observed after DNA relaxation, and further depend on the growth phase. We characterised these genes at the functional level, and also detected distinct patterns in their spatial and orientational organisation along the chromosome. Altogether, these results suggest that the "supercoiling-sensitivity" is not an intrinsic property of promoters, but depends on the action of specific topoisomerases, on the physiological conditions, and on their genomic context. Based on previous in vitro expression data of several promoters, we propose a qualitative model of SC-dependent regulation that accounts for many of the contrasting transcriptomic features observed after gyrase or topoisomerase I inhibition.
The catabolism of pectin from the plant cell walls plays a crucial role in the virulence of the phytopathogen Dickeya dadantii. In particular, the timely expression of pel genes encoding major pectate lyases is essential to circumvent the plant defense systems and induce a massive pectinolytic activity during the maceration phase. While previous studies identified the role of a positive feedback loop specific to the pectin degradation pathway, here we show that the pel> expression pattern is controlled by a metabolic switch between glucose and pectin. We develop a dynamical and quantitative regulatory model of this process integrating the two main regulators CRP and KdgR related to these two sources of carbon, and reproducing the concentration profiles of the associated metabolites, cAMP and KDG respectively, quantified using a new HPLC method. The model involves only 5 adjustable parameters, and recapitulates the dynamics of these metabolic pathways during bacterial growth together with the regulatory events occurring at the promoters of two major pel genes, pelE and pelD. It highlights their activity as an instance of carbon catabolite repression occurring at the transcriptional regulatory level, and directly related to the virulence of D. dadantii. The model also shows that quantitative differences in the binding properties of common regulators at these two promoters resulted in a qualitative different role of pelD and pelE in the metabolic switch, and also likely in conditions of infection, explaining their evolutionary conservation as separate genes in this species.
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