An ex vivo model for understanding the impact of vaccination on Mycobacterial persister populations
Led by Prof Samantha Sampson (Stellenbosch University, South Africa), with Asst Prof Andrea Zelmer (LSHTM, UK) and Dr Jomien Mouton (Stellenbosch University, South Africa)
Project Aims
Tuberculosis (TB) is a devastating disease worldwide. The available drugs, vaccines and tools for diagnosing the disease are sub-optimal, and more understanding of the bacterium that causes TB is needed. In particular, we need a better understanding of latent TB, a state in which the bacteria are thought to become "dormant", and are called "persisters". In this state, they are able to escape killing by conventional TB drugs, and survive within the host, but may later reawaken to cause active disease. In this study, we will investigate how the current vaccine against TB may influence the formation of these persister bacteria. To achieve this, we will use a special form of TB bacteria that express fluorescent proteins that tell us when the bacteria are in a persister state. We will use these specialised "reporter" bacteria to infect cells taken from vaccinated and non-vaccinated mice, and then characterise the host and bacterial cells within these samples. The results obtained could provide new insights into how host factors influence persister formation, and vice versa. This would help to rationally design new vaccines and therapies that reduce persister formation and therefore increase long-term protection against TB.
Project Outcomes
Tuberculosis (TB) is a devastating disease worldwide. The available drugs, vaccines and tools for diagnosing the disease are sub-optimal, and more understanding of the bacterium that causes TB is needed. In particular, we need a better understanding of latent TB, a state in which the bacteria are thought to become “dormant”, and are called “persisters”. In this state, they are able to escape killing by conventional TB drugs, and survive within the host, but may later reawaken to cause active disease.
The VALIDATE pump-priming funding has allowed us to lay the foundation for work aimed at determining how the current vaccine against TB may influence the formation of these persister bacteria. To achieve this, we have used a special form of TB bacteria that express fluorescent proteins that tell us when the bacteria are in a persister state. We have optimised methods that will allow us to more rapidly determine how these specialised “reporter” bacteria respond when used to infect cells taken from vaccinated and non-vaccinated mice. We have developed recorded training videos that will allow others to learn how to perform the key techniques involved in this work.
Work on this project is still ongoing, and we expect that the results obtained could provide new insights into how host factors influence persister formation, and vice versa. This would help to rationally design new vaccines and therapies that reduce persister formation and therefore increase long-term protection against TB.
