Sunday, 31 August 2008

Signal jamming

A compound that acts like a jamming device, preventing bacteria from detecting host signalling and bacterial signaling, provides promise for a broad-spectrum approach to treating bacterial infection.

At least 25 bacteria succeed as pathogens, in part, because they can spy on their hosts and communicate with other bacteria. When bacteria detect certain signals, they respond by expressing bacterial proteins that increase their virulence. Sperandio and colleagues now report that they can reduce the effects of bacterial infection by jamming the bacterial signal decoder.

Sperandio and colleagues found that a small molecule, dubbed LED209, binds QseC, the bacterial protein that normally detects external signalling. LED209-treatment not only prevented the upregulation of virulence genes in infected cultured cells, it also protected animals against Esherichia coli, Salmonella typhimurium and Francisella tularensis in animal models. For example, 9 days after innoculation with F. tularensis, 80% of LED209-treated mice were still alive, compared with only 10% of untreated mice.

Although bacteria tend to evolve resistance to drugs that affect bacterial health, LED209 does not have adverse effects on bacterial health, but just prevents the expression of virulence proteins. Consequently, bacteria are less likely to develop resistance to LED209 and similar drugs, suggesting that that such drugs could make excellent broad-spectrum antibiotics.