2020YXFSW5

Helicobacter pylori is one of the most common human pathogens worldwide, recognized as the causative agent of peptic ulcer and malignant gastric cancer. Due to an increasing rate of antibiotic resistance, the currently available therapies for H.pylori are beginning to lose efficacy. The H.pylori gene hp1043 encodes the essential transcriptional regulator HP1043, which orchestrates all important cellular processes. We propose to characterize HP1043 and identify molecules able to disrupt HP1043 function and block H.pylori infection. We have generated and validated a structural model of HP1043 interacting with DNA to carry out virtual screening of libraries of molecules, thereby blocking its regulatory activity. Identified molecules will be experimentally validated both in vitro on the purified protein and in vivo by using E.coli reporter strains and on H.pylori cell cultures. Obtained results will offer an in-depth understanding of HP1043 regulatory mechanism and of its role in pathogenesis, as well as a further step towards the design of novel molecules able to block H.pylori infection.