Drugs to be screened via zebrafish infection models
Pathogenic microorganisms have evolved sophisticated strategies to overcome their host’s immune systems, resulting in the death and disability of millions of people. Understanding the mechanisms underlying host-pathogen interactions will help combat such diseases and develop better strategies for drug discoveries. The EU-funded FISHFORPHARMA (Training network on zebrafish infection models for pharmaceutical screens) project was established to develop zebrafish infectious disease models and to identify new drug targets for infectious disease treatment. It also equipped young researchers with the requisite knowledge and skills to achieve these goals. Zebrafish produce a large number of transparent embryos, making them ideal for live imaging of human infectious disease processes, including tuberculosis and hospital acquired infections. Thus, project partners optimised and standardised zebrafish models to study bacterial and viral infections in different tissues. They also developed a new zebrafish infection model for protozoan blood parasites. Results included improved procedures for bacterial, viral and parasitic infection models and tools for visualising host-pathogen interactions and analysing host immune responses. Researchers achieved a better understanding of pathogenicity mechanisms in human infectious diseases. In addition, FISHFORPHARMA developed high-throughput methods based on a robotic infection system. This was successfully used in anti-tuberculosis drug screening and can also be extended to models of Staphylococcal diseases. FISHFORPHARMA has helped develop more efficient methods for antimicrobial drug screening, which are urgently needed to combat the increasing incidence of antibiotic resistance. The introduction of a pre-screening phase using zebrafish embryos in the drug discovery pipeline could reduce subsequent screening in rodent models, thereby increasing the speed of drug discovery.
Keywords
Zebrafish, infection models, host-pathogen interaction, FISHFORPHARMA, protozoan blood parasites, tuberculosis, Staphylococcal diseases, viral diseases, drug discovery
