title: CbpA acts as a modulator of HspR repressor DNA binding activity in Helicobacter pylori.
abstract: The ability of pathogens to cope with disparate environmental stresses is a crucial feature for bacterial survival and for the establishment of a successful infection and colonization of the host; in this respect, chaperones and heat shock proteins (HSPs) play a fundamental role in host-pathogen interactions. In Helicobacter pylori, the expression of the major HSPs is tightly regulated through dedicated transcriptional repressors (named HspR and HrcA), as well as via a GroESL-dependent posttranscriptional feedback control acting positively on the DNA binding affinity of the HrcA regulator itself. In the present work we show that the CbpA chaperone also participates in the posttranscriptional feedback control of the H. pylori heat shock regulatory network. Our experiments suggest that CbpA specifically modulates HspR in vitro binding to DNA without affecting HrcA regulator activity. In particular, CbpA directly interacts with HspR, preventing the repressor from binding to its target operators. This interaction takes place only when HspR is not bound to DNA since CbpA is unable to affect HspR once the repressor is bound to its operator site. Accordingly, in vivo overexpression of CbpA compromises the response kinetics of the regulatory circuit, inducing a failure to restore HspR-dependent transcriptional repression after heat shock. The data presented in this work support a model in which CbpA acts as an important modulator of HspR regulation by fine-tuning the shutoff response of the regulatory circuit that governs HSP expression in H. pylori.
authors.affiliation: Department of Biology, University of Bologna, Via Selmi 3, 40126 Bologna, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Roncarati
authors.forename: Alberto
authors.initials: A
authors.lastname: Danielli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Scarlato
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D006360:Heat-Shock Proteins; C108444:HspR protein, bacteria; D018832:Molecular Chaperones; D012097:Repressor Proteins