Molecules that dominate bacterial secretion created

Chemists have created molecules that mimic and dominate the toxic molecules secreted by bacteria.

A research team at Syracuse University in the US used the bacteria Pseudomonas aeruginosa to create molecules that can control the chemical signalling of molecules secreted by bacteria. They believe their findings could allow the development of new drug molecules.

“Using toxic molecules to develop therapeutic agents, such as a vaccine, is not easy. We’re just beginning to understand how some molecules – synthetic or naturally occurring – control the activities of bacteria. This will help us develop, among other things, drugs with many different applications,” said Associate Professor of chemistry Yan-Yeung Luk at Syracuse University.

The chemists studied molecules called rhamnolipids – molecules with sugar rings and fatty acids that can reduce the surface tension of water – secreted by P. aeruginosa bacteria and designed a class of molecules that can control their chemical signals. The new designed molecules – synthetic disaccharide derivatives (DSDs) – can control activities such as biofilm formation, bacterial adhesion and swarming motility.

“Biologists know how rhamnopilids are made by bacteria, and can knock out their production, but they don't fully understand how rhamnolipids work – specifically, how they control different types of bacterial activities,” said Luk.

The results, published in the journal ChemBioChem, showed that a subset of DSDs dominate the function of rhamnolipids and demonstrated capacity for a range of new, unexpected bioactivities. One of these bioactivities is phenotypic switching in which bacteria abandon their original phenotypes to “change” into two different phenotypes. The chemical was also shown to affect bacterial adhesion, considered the first step in colonisation and biofilm formation.

“By determining the important structural features of DSDs, we've figured out how to control the behaviour of P. aeruginosa. At the same time, DSDs have enabled a series of novel biological phenomena that are starting to reveal how rhamnolipids work – something that has baffled scientists for a long time. It's exciting to be on the brink of discovery,” said Luk.

The team have designed and synthesised a chemical library of molecules that contained two DSDs whose structures dominated the functions of rhamnolipids.  They believe these molecules may offer the potential for many applications.

Paper: http://onlinelibrary.wiley.com/doi/10.1002/cbic.201500396/abstract