Scientists Trick Bacteria with Small Molecules

A team of Yale University scientists has engineered the cell wall of the Staphylococcus aureus bacteria, tricking it into incorporating foreign small molecules and embedding them within the cell wall.

The finding, described online in the journal ACS Chemical Biology this week, represents the first time scientists have engineered the cell wall of a pathogenic “Gram-positive” bacteria—organisms responsible not only for Staph infections but also pneumonia, strep throat and many others. The discovery could pave the way for new methods of combating the bacteria responsible for many of the most infectious diseases.

The team engineered one end of their small molecules to contain a peptide sequence that would be recognized by the bacteria. In Staphylococcus aureus, an enzyme called sortase A is responsible for attaching proteins to the cell wall.

“We sort of tricked the bacteria into incorporating something into its cell wall that it didn’t actually make,” said David Spiegel, a Yale chemist who led the study. ... By being able to manipulate the cell wall, we can in theory perturb the bacteria’s ability to interact with human tissues and host cells.” ...

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