Breaking up the Superbugs’ Party
News Aug 16, 2013
A BBSRC-funded multi-disciplinary research team at the University's Centre for Biomolecular Sciences has uncovered a new way of inhibiting the toxicity and virulence of the notorious superbug, Pseudomonas aeruginosa.
These bacteria are resistant to many conventional antibiotics. It is almost impossible to eradicate P. aeruginosa from the lungs of people with cystic fibrosis and is therefore a leading cause of death among sufferers. The bug also causes a wide range of infections particularly among hospital patients.
The new discovery concerns the bacterial cells' ability to 'talk' to each other by producing and sensing small chemical signal molecules. This is called 'quorum sensing' (QS) and enables a population of individual bacteria to act socially rather than as individuals. QS allows a population of bacteria to assess their numerical strength and make a decision only when the population is 'quorate'.
The mechanism through which QS signals work is by activating gene expression upon interaction of a QS signal molecule with a receptor protein. In many disease-causing bacteria, QS controls genes which are essential for infection. These genes code for virulence factors such as toxins which cause damage to host tissues and the immune system. Interfering with the QS signalling process blocks bacterial virulence and renders bacteria unable to cause infection. Consequently QS systems are molecular targets for the development of new anti-infective drugs which do not kill bacteria but instead block their ability to cause disease.
In a study published in the journal, PLOS Pathogens, the Nottingham team has described how they solved the 3D structure of a receptor protein called PqsR used by P. aeruginosa to sense alkyl quinolone QS signal molecules so that they could visualize the shape of the QS signal molecule-binding site within the PqsR protein.
Professor of Molecular Microbiology, Paul Williams, said: "We were able to synthesize and screen a library of chemical compounds which could fit within the PqsR binding site and block receptor activation by the QS signal molecules. The active compounds were screened for their ability to inhibit QS and through a process of chemical refinement some novel potent QS inhibitors were discovered which were tested biologically on P.aeruginosa and shown to block virulence gene expression."
Professor of Macromolecular Crystallography, Jonas Emsley, added: "This ground-breaking work establishes a platform for the future evaluation and further development of these new QS inhibitor compounds as potential drugs for the treatment of P. aeruginosa infections."
Can You Eat Cells? Computer Model Predicts Organisms that Use PhagocytosisNews
A computer model developed by Museum researchers may provide new insight into the origins of phagocytosis, the process by which single-celled organisms “eat” other cells as a means of absorbing nutrients or eliminating pathogens.READ MORE
‘Lipid Asymmetry’ Plays Key Role in Activating Immune CellsNews
Regulating the lipid and physical asymmetry of a cell’s membrane is critical to immune cell function, and researchers have now shown that by preventing loss of membrane asymmetry it’s possible to control the immune response.READ MORE
Studying Ebola-Host Cell Interaction Helps Find Targets for Antiviral DrugsNews
In some ways, the Ebola virus operates like a vampire; only after it is politely invited in to a host cell does it take up the task of destroying everything in its path. In a new study researchers seek to elucidate quantitatively the biomechanical mechanism of Ebola-host cell interaction, providing potential new targets for antiviral drug development.READ MORE
Comments | 0 ADD COMMENT
World Advanced Therapies & Regenerative Medicine Congress
May 16 - May 18, 2018