Mystery of Bacterial Growth and Resistance Resolved ?

In continuation of my update on the mechanism of bacterial resistance...

Scientists at The Scripps Research Institute have unraveled a complex chemical pathway that enables bacteria to form clusters called biofilms. Such improved understanding might eventually aid the development of new treatments targeting biofilms, which are involved in a wide variety of human infections and help bacteria resist antibiotics. 

Biofilm formation is a critical phenomenon that occurs when bacterial cells adhere to each other and to surfaces, at times as part of their growth stage and at other times to gird against attack. In such aggregations, cells on the outside of a biofilm might still be susceptible to natural or pharmaceutical antibiotics, but the interior cells are relatively protected. This can make them difficult to kill using conventional treatments.

Past research had also revealed that nitric oxide is involved in influencing bacterial biofilm formation. Nitric oxide in sufficient quantity is toxic to bacteria, so it's logical that nitric oxide would trigger bacteria to enter the safety huddle of a biofilm. But nobody knew precisely how. In the new study, the scientists set out to find what happens after the nitric oxide trigger is pulled. "The whole project was really a detective story in a way," said Plate.

To learn more, the researchers used a technique called phosphotransfer profiling. This involved activating the histidine kinase and then allowing them to react separately with about 20 potential targets. Those targets that the histidine kinase rapidly transferred phosphates to had to be part of the signaling pathway.

"It's a neat method that we used to get an answer that was in fact very surprising," said Plate. 

The experiments revealed that the histidine kinase phosphorylated three proteins called response regulators that work together to control biofilm formation for the project's primary study species, the bacterium Shewanella oneidensis, which is found in lake sediments.

Further work showed that each regulator plays a complementary role, making for an unusually complex system. One regulator activates gene expression, another controls the activity of an enzyme producing cyclic diguanosine monophosphate, an important bacterial messenger molecule that is critical in biofilm formation, and the third tunes the degree of activity of the second.

Since other bacterial species use the same chemical pathway uncovered in this study, the findings pave the way to further explore the potential for pharmaceutical application. As one example, researchers might be able to block biofilm formation with chemicals that interrupt the activity of one of the components of this nitric oxide cascade.

Ref : http://www.scripps.edu/news/press/2012/20120426marletta.html

http://www.sciencedirect.com/science/article/pii/S1097276512002602