Under pressure: new research programme to examine how bacterial pathogens cope with stress

BBSRC grant fuels interdisciplinary bacterial stress response research - News

By Danielle Reeves
Thursday 30 July 2009

A new cross-faculty research programme to investigate how dangerous bacterial pathogens manage to survive in the stressful environment of the human body has been launched at Imperial College London, thanks to a £3 million grant from the Biotechnology and Biological Sciences Research Council (BBSRC).

The four-year programme will focus on E. coli, a common bacterium that is usually harmless but can cause severe vomiting and diarrhoea, and Mycobacterium tuberculosis, the bacterial pathogen that causes tuberculosis in humans.

E. coli cells with the stress-adaptation signalling regions highlighted

The researchers' aim is to gain a better understanding of how these and other bacterial pathogens adapt to the environmental stresses they encounter – such as changes in temperature, acidity and the level of different nutrients – when they infect a human host.

They hope that revealing in detail the survival mechanisms used by bacterial cells could one day lead to new medical treatments that disrupt or override this process, leading to the death of the pathogen and curing the host.

Principal Investigator of the new project, Professor Martin Buck, joint Head of Imperial's Division of Biology, explains: "One of the reasons these and other bacterial pathogens are so good at making us sick is that they are very good at adapting to multiple potentially harmful changes in their environment at the same time. This means they can survive for a long time in the testing environment of our lungs or our gut, causing often severe sickness and even death.

We're hoping to uncover the detailed networks of molecular chain reactions that happen inside each bacterial cell when it responds to stress, with long term aim of finding ways to undermine these survival skills and therefore treat the diseases they cause."

It is already known that bacterial pathogens including E. coli and Mycobacterium tuberculosis respond to environmental stresses by turning different genes on and off over the course of their lifetime, allowing them to adapt to different environmental conditions as they encounter them. However, the chain of events that occurs inside the bacterial cell from the moment the external stress is perceived, to the eventual changes in gene expression, is far from fully understood. This understanding is, however, crucial for designing new medical treatments.

Professor Buck and his colleagues from Imperial's Faculties of Natural Sciences, Engineering and Medicine hope to map out this chain of events in detail. They will also use mathematical modelling techniques to build a clearer picture then ever before of how bacterial cells are able to carry out many adaptations simultaneously.

One of their large-scale experiments will focus on E. coli's response to changes in the quality and amount of simple and complex nitrogen-containing molecules that are available to it. The bacteria are often faced with a varying supply of these types of nitrogen sources during the course of infection and transmission.

The bacteria need these nitrogen-containing molecules in order to survive, but they also need to adapt to variations in their supply in order to utilise them. Whether and how they can adapt when facing additional stresses is unknown. The research team will carry out a number of detailed analyses of E. coli's response to changes in the nitrogen available in its environment, and will investigate whether or not the bacterium is still able to survive in these conditions if its signalling pathways are disrupted.

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