NOVEL MOLECULAR MECHANISMS UNDERLYING PATHOGEN KILLING IN MACROPHAGES

Antibiotics have been used to treat bacterial infections for the past century and have significantly contributed to the increase in life expectancy over this period. However, the past few decades have seen a dramatic increase in bacterial resistance to antibiotic treatment. The emergence of antibiotic resistance is creating major difficulties in the treatment of many bacterial diseases, and novel approaches to kill infecting bacteria are desperately required.

Most healthy people with an efficient immune system are well equipped to defeat the majority of bacterial infections. Understanding exactly how our immune system recognizes and kills bacteria will therefore help identify new ways to fight bacterial infections efficiently and enhance the potential of our immune system. Macrophages are important cells in our immune system, whose main function is to eat, kill and digest microbes such as bacteria. But how macrophages do this is only partially understood.

Salmonella enterica is a major bacterial pathogen. There are more than two thousand different types (serovars) of Salmonella enterica that cause serious infections in humans, farm animals and pets. These pathogens are becoming increasingly resistant to antibiotics, making them a serious global health threat. We recently identified two molecular components essential for macrophages to kill Salmonella enterica. In this project we will investigate these antimicrobial molecules, taking advantage of state-of-the-art tools and expertise available in our laboratory. Central to this project are advanced technologies that will allow us to identify specific molecules from complex cellular extracts ("omic" technologies) that contribute to pathogen killing. Understanding the role of these novel antimicrobial molecules and associated proteins, which are used by macrophages to kill bacteria, will represent a significant breakthrough in the understanding of the function of the immune system. The insights we obtainwill be fundamental to the identification of ways to enhance the molecular antimicrobial activities of macrophages and boost immune responses in both humans and farm animals.