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Chemical Biology

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Bacteria come unstuck


14 February 2007

Forcing bacteria to go bald could help to combat infections.

"This is a terrific example of the application of chemical biology to manipulate organelle biosynthesis in bacteria with a clear relevance to biomedicine."
- Douglas Weibel

Researchers at Umeå University, Sweden, and Washington University in St Louis, US, have studied how the hair-like pili on a bacterium's surface can be reduced using chemicals called pilicides. 

Pili are made of proteins and help bacteria bind to cells. Fredrik Almqvist and co-workers had already established that pilicides disrupt pili formation in Escherichia coli. Now, they have found that pilicides do this by limiting the number of pili formed, but without affecting their physical properties. The team showed that when individual pili are grown in solutions containing pilicides they have the same structural and biomechanical properties as normal pili. Their component proteins are correctly folded and anchored to the bacterial cell surface.

Scheme showing suppression of the expression of pili in E. coli by pilicide treatment

Pilicides reduce the number of hair-like pili on bacteria, but do not change their physical properties

The researchers suggested that pilicides suppress the number of pili by affecting molecular chaperones, proteins or protein complexes that help assemble the pili structures.

By reducing the number of these hair-like assemblies, pilicides reduce a bacterium's ability to stick to a surface, such as a cell wall. For some types of bacteria, such as uropathogenic strains of E. coli, this pili-cell binding plays an important role in infection. Almqvist said that pilicides allowed researchers to 'investigate how bald a bacterium could be, and still be infectious' and 'the goal was to eventually create new antibiotics'. 

Pilicides will be 'invaluable tools for dissecting the role of pili in the adhesion of cells to surfaces and the infection of host tissues by bacteria,' said Douglas Weibel, a biochemist at University of Wisconsin-Madison, US. 'This is a terrific example of the application of chemical biology to manipulate organelle biosynthesis in bacteria with a clear relevance to biomedicine,' he added.

Russell Johnson

Link to journal article

Pilicides regulate pili expression in E. coli without affecting the functional properties of the pilus rod
Veronica Åberg, Erik Fällman, Ove Axner, Bernt Eric Uhlin, Scott J. Hultgren and Fredrik Almqvist, Mol. BioSyst., 2007, 3, 214
DOI: 10.1039/b613441f

Also of interest

Pilicides—small molecules targeting bacterial virulence
Veronica Åberg and Fredrik Almqvist, Org. Biomol. Chem., 2007, 5, 1827
DOI: 10.1039/b702397a