Dr Nastassja Kriel, Stellenbosch University - VALIDATE Fellow
Identifying persister Mycobacterium tuberculosis biosignatures
Mycobacterium tuberculosis causes tuberculosis (TB) in people worldwide. The only TB vaccine available is only effective in preventing disease in children with diminishing effects over time. Infection and treatment of TB can result in the formation of bacterial sleeper cells, known as persisters. Persisters can survive antibiotic treatment and resume growth, resulting in the reoccurrence of disease after treatment. Persister bacteria are unique because the resistance they have to treatments is not caused by DNA changes. However, very little is known about how these bacteria influence the cells which protect the body against infections, allowing them to survive.
Bacteria export proteins out of the cell to re-program the body's defence systems and allow survival of persister bacteria. I will investigate which proteins are secreted by persister TB bacteria to re-program human defence cells for their long-term survival. I will go on to investigate which proteins are produced by human defence cells in response to infection with persister TB bacteria. I will do this by making use of a special form of TB, which when forming persister TB, makes red proteins. We will isolate these red TB bacteria and use state of the art molecular techniques and sophisticated computational analyses of data to provide new insights on how persister TB interact with human defence cells and how these cells respond to infection. Understanding the host-pathogen interactions between human defence cells and TB will provide new insights into how we can prevent persister formation. The identification of persister TB exported proteins will provide new anti-TB vaccine candidates, which target dormant infections and could provide long-term protection against TB.
Find out more about Dr Nastassja Kriel here.