A 2018/2019 Summer Studentship research project
Mycobacterium tuberculosis kills more than 4,000 people every day and as multidrug resistance increases this number may rise. Understanding how the bacterium resists killing by neutrophils may provide new therapeutic strategies to assist the immune system.
Student: Health Ryburn
Supervisor: Professor Mark Hampton, Dr Heather Parker
The bacterium Mycobacterium tuberculosis is a major human pathogen. Despite established diagnostic tests and treatments, the incidence of tuberculosis remains high and multidrug resistance is becoming a serious problem. In order to develop new therapeutics, we need to better understand how M. tuberculosis evades the immune system. Recent evidence implicates the neutrophil as a potential site for bacterial replication. In preliminary experiments we have discovered the closely-related bacterium M. smegmatus is rapidly phagocytosed by human neutrophils, and the neutrophil generates a burst of reactive oxidants in an effort to kill the bacterium, but there is a limited degree of oxidant-dependent killing.
The aim of this project is to assess the resistance of M. smegmatus to neutrophil oxidants, and explore if it is possible to sensitise this bacterium to oxidative stress.
Non-pathogenic M. smegmatus will be cultured in the laboratory, exposed to the oxidant hypochlorous acid, and survival assessed by colony counting. The sensitivity of this bacterium will be compared by other species known to be rapidly killed by neutrophils. A selection of mutant M. smegmatus strains in which selected antioxidant proteins have been knocked out will also be assessed. Bacteria will also be incubated with neutrophils isolated from human blood to correlate oxidant-sensitivity to killing by neutrophils.
Student researcher’s component of the study
The student will be responsible for all of the laboratory work undertaken for this project.