Drug Discovery Opinion

Quorum sensing is used by bacteria to coordinate gene expression according to local population densities. The bacteria secrete signalling molecules and have receptors that can specifically recognize signalling molecules released by other bacteria of the same or different species. When the concentration of the signalling molecule reaches a certain concentration (i.e. many bacteria in the location), a response is triggered.

In 2006, researchers at UT Southwestern Medical Center described how blocking a newly discovered receptor in a strain of E. Coli could prevent infection. When contaminated food containing a virulent strain of E. Coli is eaten, the bacteria cause no damage until they encounter signalling molecules produced by native gut flora together with the human hormones, adrenaline and noradrenaline. These molecular signals prompt the virulent E.Coli bacteria to release enterotoxins which, in extreme cases, can be fatal.

In a recent report in the journal Science, Dr Sperandio’s group now describe the activity of a small molecule, LED209, which doesn’t inhibit bacterial growth but which markedly inhibits the virulence of several bacterial strains, both in vitro and in infected animals.

Many bacterial pathogens rely on signalling pathways using the same “adrenergic-type” receptor to promote the expression of virulence factors, so inhibition of this pathway may offer a strategy for the development of new broad-spectrum antimicrobial drugs. It is also possible that antagonists of this signalling pathway may not give rise to the widespread resistance seen with traditional antimicrobial agents.

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