Molecular Biology and Genomics of Prokaryotes. Coordinator: Scarlato

The research group studies regulation of gene expression in Helicobacter pylori, the human pathogen responsible for various gastric diseases. The main objective is to understand the molecular mechanisms controlling transcription of virulence genes in response to environmental changes.

Areas: Genomics

Helicobacter pylori is an important human pathogen, recognized by the World Health Organization as a class I carcinogen.

The ability of this Gram-negative bacterium to colonize the hostile stomach niche and to establish a persistent infection depends on the coordinated expression of virulence factors that allow the pathogen to adapt to adverse environmental conditions and to counteract the defense mechanisms of the host. The research carried out by our group combines biochemical, genetic and molecular biology methodologies to study the molecular mechanisms adopted by two transcriptional repressors involved in the heat-shock response, HrcA and HspR, and of a response regulator called HP1043, essential for vitality of the bacterium and involved in the regulation of crucial cellular processes.

Research themes

Transcriptional Control in Response to Heat-shock:

The heat-shock response in the human pathogen H. pylori is governed by two transcriptional repressors, HrcA and HspR. These regulators, under normal growth conditions maintain the repression of the main heat-shock genes and, following thermal shock, allow a rapid and transient accumulation of the regulated transcripts. Our group studies the molecular mechanisms exerted by each regulator and their interactions to control transcription of genes in response to temperature fluctuations.

Transcriptional Control by the Essential Regulator HP1043:

The HP1043 transcriptional regulator is encoded by a gene essential for the vitality of the bacterium. The inability to generate a deletion mutant for the hp1043 gene or to modulate the protein levels of the regulator in vivo has so far precluded the understanding of its function. Through chromatin immunoprecipitation assays (ChIP), we identified 37 promoters bound in vivo by HP1043 at the genomic level that allowed the identification of the DNA-binding consensus sequences in vitro. We study the molecular mechanisms of in vitro transcription activation by identifying the determinants of DNA binding specificity and the effects on its ability to activate transcription.

Lab members

Prof. Davide Roncarati, https://www.unibo.it/sitoweb/davide.roncarati/en

Anna Maria Zannoni, PhD student

Federico D'Agostino, PhD student

Luigia Cappelli, PhD student

Paolo Cinelli, PhD student

Internship projects

none

Main publications

Roncarati D, Scarlato V. (2017). “Regulation of heat-shock genes in bacteria: from signal sensing to gene expression output.” FEMS Microbiol Rev. 41(4):549-574. https://www.ncbi.nlm.nih.gov/pubmed/28402413.

Roncarati D, Pinatel E, Fiore E, Peano C, Loibman S, Scarlato V. (2019). “Helicobacter pylori Stress-Response: Definition of the HrcA Regulon.” Microorganisms 7(10). pii: E436. https://www.ncbi.nlm.nih.gov/pubmed/31614448

Pelliciari S, Pinatel E, Vannini A, Peano C, Puccio S, De Bellis G, Danielli A, Scarlato V, Roncarati D. (2017). “Insight into the essential role of the Helicobacter pylori HP1043 orphan response regulator: genome-wide identification and characterization of the DNA-binding sites.” Sci Rep. 7:41063. https://www.ncbi.nlm.nih.gov/pubmed/28112213

Contacts