KILLINGTYPHI · Identification of host-factors restricting Salmonella Typhi

Identification of host-factors restricting Salmonella Typhi

Salmonella enterica serovar Typhi (S. Typhi) is one of the thousands of Salmonella types that exists. In contrast to other Salmonella species that can infect a broad range of vertebrate hosts and cause self-limited gastrointestinal infections in humans, S. Typhi is an unique serovar only able to infects humans (host-restriction). This bacterium causes a life-threatening systemic disease known as typhoid fever that affects more than 26 million people and kills over 200,000 patients annually. Typhoid is acquired by consumption of contaminated water or food washed in contaminated water and the incidence is particularly high in developing countries, where the disease spreads widely due to poor water sanitation and hygiene conditions. Natural disasters such as flooding or earthquakes can dramatically increase the risk of typhoid epidemics. Although this illness is commonly associated with low income regions, there are cases of typhoid in Western countries. These cases are associated with traveller returning from areas where typhoid is common. After antimicrobial treatment, some patients (called carriers) continue to, asymptomatically, carry and to spread S. Typhi being a source of infection for other people. Current typhoid vaccines have limitations, since they do not provide complete protection or lasting immunity. In addition, multidrug resistant S. Typhi are spreading globally making this illness almost untreatable in many areas of the planet. For all of this, typhoid is a global health problem and it is urgent to identify novel therapeutics to treat this disease. This requires a better understanding on how the host responds to S. Typhi infection and how the bacterium overcomes host defences. S. Typhi can live inside macrophages - cells of the immune system devoted to kill pathogens. Unlike human macrophages, macrophages from animals are able to clear S. Typhi. In 2012 Spanò and Galán identified two molecules in mice that are essential to kill S. Typhi. In spite of this, the exact killing mechanisms used by macrophages remain unknown. The overall objective of this project was to identify all the mechanisms that the macrophage uses to fight S. Typhi infection. For this, our first aim was to optimize the conditions for a large genome scale analysis in a smaller scale, targeting gene families that are known to be exploited by Salmonella and other bacterial pathogens to cause disease. In addition, we chose factors known to have an impact in the survival of bacterial pathogens in macrophages and evaluated their role in the outcome of S. Typhi infection.

Data: CORDIS, © European Union