Bridging the Gaps: Systems-level approaches to antimicrobial resistance
Exploiting the potential of Raman Microscopy for real-time molecular imaging of quorum sensing activation and inhibition in situ in planktonic bacterial cells and biofilms
Paul Williams (Life Sciences), Ioan Notingher (Physics and Astronomy) and Faris Sinjab (Physics and Astronomy)
Conventional antibiotics mostly function by killing bacteria, but this increases the selective pressure on bacteria and can lead to increased resistance to antibiotics. Bacteria also cause tissue damage and disease as they deploy their virulence factors e.g. by releasing toxins to weaken the host’s immune system. If we were able to disable the bacterium’s virulence factors instead of killing them, it may be possible to treat infection without increasing resistance and reduce damage to humans and other animals.
To develop such treatments we would need a more thorough understanding of the physiology and molecular biology of pathogenic bacteria. One promising target for such investigation is quorum sensing (QS) – the molecular signals that tell bacterial populations they have reached sufficient numbers for their virulence factors to be effective. However, at the moment we have little understanding of how QS signal molecules move between bacterial cells.
In order to gain new insight into the biophysics of this mechanism, we will use confocal Raman Microscopy. Though a previous experiment using these techniques has been undertaken, it required the bacterial colonies to be established on an invasive substrate to enhance the signal. In these experiments the cells will instead be alive, and use new techniques in high-resolution Raman imaging to overcome previous issues. This will allow us real-time insights into QS signal molecule exchange.
By understanding the transfer of QS signal molecules, we could begin to create ways to block, interfere with and alter their transmission, and so delay or completely abort the deployment of virulence factors. This would allow for new antibacterial drugs that “shut down” the infection, rather than killing the bacteria, and so reduce resistance.
If you are interested in finding out more about this research or about Bridging the Gaps please be in contact with Harry Moriarty firstname.lastname@example.org in the first instance.