Project Portugal 2030

Summary

The primary goals of this project are to characterize in detail the structure-function relationship of PBT, a virulence-associated toxin from Photobacterium damselae subsp. piscicida, and to dissect its molecular and cellular mechanisms of intoxication. Through this investigation, we aim to obtain essential knowledge required to develop a toxin-based vaccine able to protect fish against this pathogen. By disclosing the molecular details underlying PBT intoxication, we also seek to set the basis for future development of anti-virulence therapies to treat Phdp infections. This will result in decreased antibiotic usage in fish farms, lowering the risks associated with emergence and spreading of antibiotic resistance. By positively impacting this critical public health issue, this project aligns with the strategies under the One Health framework, which considers the health of humans, animals, and the environment as interconnected. Furthermore, we intend to investigate whether PBTb homologues found in various human and animal pathogens share structural and functional similarities with PBT, as this may lead to discovery of novel virulence factors in these pathogens, suitable to be explored for vaccination or drug design purposes. To achieve these objectives, our project will: 1. Identify the receptor-binding domain of PBT and the structural elements necessary for interaction with host cells. 2. Investigate whether PBT intoxication involves pore formation at the cytoplasmic membrane or requires internalization of the toxin. 3. Evaluate the vaccine potential of PBT domains and detoxified versions of PBT 4. Define the structure and toxicity profiles of representative PBT homologues found in animal and human pathogens The accomplishment of these objectives will contribute to high-impact publications in leading scientific journals, enhancing the international visibility and recognition of the research team within the scientific community, and will provide innovative solutions of high interest to the aquaculture industry. Moreover, we aim to strengthen and expand international collaborations, fostering partnerships with renowned researchers and institutions beyond the project timeline, which will further promote the internationalization of the research team and of the proponent institution. Additionally, this project will nurture the development of next-generation scientists, by offering training opportunities and fostering an environment conducive to learning and professional growth.