Summary of the Keystone Symposia on Molecular and Cellular Biology:

New Developments in Our Basic Understanding of Tuberculosis

by Cameron Lack

In January 2017, with the generous travel funding of INTEGRATE AMR, I attended the Keystone Symposia for New Developments in Our Basic Understanding of Tuberculosis (TB).

TB is an endemic contagious disease in many countries around the world and ranks alongside HIV as the leading cause of death due to infectious disease. Over the past twenty years there has been substantial effort to develop new vaccines and antibiotics, however new discoveries in our understanding of host-pathogen interactions, susceptibility and immunity have fallen behind clinical trials and the development of the disease. The appearance of multi-drug resistant TB (MDR-TB) and extensively-drug resistant TB (XDR-TB) over the last ten years has increased our need for new treatments and a vaccine that fully protects against the disease into adulthood.

A key feature of Mycobacterium tuberculosis (Mtb), the causative agent of TB, is its ability to evade the immune system within structures called granulomas. Here the bacteria diversify phenotypically and display its hallmark antimicrobial resistance (AMR). Work presented by Professor Carl Nathan (Cornell University) on the first day of the conference discussed the different methods by Mtb tolerates the immune system and drug treatments and developed a strategy for overcoming these tolerances depending on which were being displayed.

Another interesting insight into the way Mtb interacts with the host was a twin study presented by Professor Mark Davis (Stanford University). One of the outcomes of this study suggested that genetics has a much lower part to play in the outcome of the disease compared to environmental effects.

Part of my own research concerns the development of a within-host model to describe the interactions between Mtb and the host's immune system. A short talk given by Dr Chiara Toniolo (École Polytechnique Fédérale de Lausanne) demonstrated her interest in collecting data to measure the extracellular growth of Mtb cells alongside macrophages (a core immune cell in the protection against TB) as well as the intracellular growth of Mtb cells within macrophages. We are interested in collaborating to look at how the applications of drugs affects these processes and how phenotypic tolerance behaves in the population as a whole. We hope to be able to develop a data-based model of these interactions and tolerances in an effort to further our understanding of the disease.

 

Image Credits: George Kubica/CDC

Mycobacterium tuberculosis culture, showing colony morphology.