Project Portugal 2030

Summary

H. pylori, classified as a class I carcinogen, is considered the major risk factor for the development of gastric cancer. The rising prevalence of antibiotic-resistant strains of H. pylori has prompted researchers to seek alternative treatment options. The main goal of the HELIPROTECT research project is to create an innovative treatment for H. pylori eradication using liposomes loaded with phage-derived lysins that will contribute to reducing the incidence of gastric cancer (see graphical abstract). Our prior knowledge about phage-encoded proteins and in the analysis of H. pylori phage genomes will be useful to achieve the first objective, which involves identifying and characterizing lysins encoded by H. pylori bacteriophages through computational methods. All phages replicating through a lytic cycle require the action of lysins to cleave the host cell’s peptidoglycan, either to allow phage entry or to allow the release of phage progeny. Since no H. pylori phage lysin has yet been reported, we hypothesize that these lysins must be distinct from the other ones, which will make their identification more challenging. Therefore, the recognition of lysins in H. pylori phages would be challenging, but of utmost importance. Secondly, proteins must be recombinantly expressed, purified and characterized (stability, structure, effectiveness) using state of the art equipment. The third goal of the HELIPROTECT project is the encapsulation of the recombinant proteins in liposomes of different compositions. To date, only a few recent studies have reported the encapsulation of phage proteins in liposomes, and, to our knowledge, none is for gastrointestinal applications. We aim to perform a thorough physical and chemical characterization of the liposomal formulations, assess their cytotoxicity, and evaluate their stability and efficacy against H. pylori using different in vitro methods that mimic real conditions. The last objective is to evaluate the efficacy and safety of the final product using an in vivo model. To achieve these objectives, it will be essential the collaboration of UMinho team members with the project consultants from the University of Porto (FEUP and i3S) with knowledge in different disciplines (phage proteins, Helicobacter pylori, biomaterials, drug delivery, mouse models). The HELIPROTECT project proposes a novel approach for H. pylori eradication using liposomes loaded with phage proteins. By utilizing computational tools and leveraging prior knowledge of phage-encoded proteins and H. pylori phage genomes, we are confident that we can overcome the challenge of lysins identification. The encapsulation of lysins in liposomes for gastric application represents an innovative use of liposomal technology. The final in vivo step is crucial for translating laboratory findings into potential clinical applications, demonstrating the project's focus on translational research. The interdisciplinary nature of this project, involving the collaboration of experts from various fields, allows for the integration of diverse perspectives and knowledge, facilitating comprehensive research and development efforts. The strategy proposed in this project represents a departure from traditional antibiotic-based therapies and offers a promising alternative for combating antibiotic-resistant strains of H. pylori.