A complex chemical pathway that enables bacteria to form clusters called bio films, unravelled by scientists at The Scripps Research Institute. 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.
The report, published online ahead of print on April 26, 2012, by the journal Molecular Cell
, explains how nitric oxide, a signaling molecule involved in the immune system, leads to biofilm formation.
"It is estimated that about 80 percent of human pathogens form biofilms during some part of their life cycle," said Scripps Research president and CEO Michael Marletta, PhD, who led the work. "In this study, we have detailed for the first time the signaling pathway from nitric oxide to the sensor through cellular regulators and on to the biological output, biofilm formation."
"There's a lot of interest right now in finding ways to influence biofilm formation in bacteria," said lead author Lars Plate, a graduate student in Marletta's team, which recently moved to Scripps Research from the University of California, Berkeley. "Figuring out the signaling pathway is a prerequisite for that."
Dangerous Get Togethers
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.
Biofilms can form on surgical instruments such as heart valves or catheters, leading to potentially deadly infections. Likewise, difficult-to-eliminate biofilms also play key roles in a host of conditions from gum disease to cholera, and from cystic fibrosis to Legionnaires' disease.
For years, the Marletta lab and other groups have been studying how nitric oxide regulates everything from blood vessel dilation to nerve signals in humans and other vertebrates. 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.