Breaking up the superbugs' party

Aug 13, 2013

The fight against antibiotic-resistant superbugs has taken a step forward thanks to a new discovery by scientists at The University of Nottingham.

A 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.

This bacteria produces an armoury of and is resistant to many conventional antibiotics. It is almost impossible to eradicate P. aeruginosa from the lungs of people with 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 ' ability to 'talk' to each other by producing and sensing small 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 and renders bacteria unable to cause infection. Consequently QS systems are 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."

Explore further: Hot-spring bacteria reveal ability to use far-red light for photosynthesis

add to favorites email to friend print save as pdf

Related Stories

Fighting bacteria's strength in numbers

May 17, 2012

Scientists at The University of Nottingham have opened the way for more accurate research into new ways to fight dangerous bacterial infections by proving a long-held theory about how bacteria communicate ...

Bacteria toxic to wound-treating maggots

Feb 04, 2010

Bacteria that infect chronic wounds can be deadly to maggot 'biosurgeons' used to treat the lesions, show researchers writing in the journal Microbiology. The findings could lead to more effective treatment of wounds and th ...

Recommended for you

How plant cell compartments change with cell growth

26 minutes ago

A research team led by Kiminori Toyooka from the RIKEN Center for Sustainable Resource Science has developed a sophisticated microscopy technique that for the first time captures the detailed movement of ...

Plants can 'switch off' virus DNA

35 minutes ago

A team of virologists and plant geneticists at Wageningen UR has demonstrated that when tomato plants contain Ty-1 resistance to the important Tomato yellow leaf curl virus (TYLCV), parts of the virus DNA ...

A better understanding of cell to cell communication

1 hour ago

Researchers of the ISREC Institute at the School of Life Sciences, EPFL, have deciphered the mechanism whereby some microRNAs are retained in the cell while others are secreted and delivered to neighboring ...

A glimpse at the rings that make cell division possible

1 hour ago

Forming like a blown smoke ring does, a "contractile ring" similar to a tiny muscle pinches yeast cells in two. The division of cells makes life possible, but the actual mechanics of this fundamental process ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

raygozak
not rated yet Aug 17, 2013
This is bound to generate resistance sooner or later.