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December 20, 2010
Preventing Bacterial Infections from Medical Devices
New research has identified a protein that helps bacteria break away from medical devices like catheters and spread throughout the body. The finding gives insight into how bacterial communities called biofilms cause disease and provides a potential target for future treatments.
Biofilms are complex, multi-layered microbial communities. They can form on biological surfaces like teeth, or on medical devices that are placed inside a patient, like catheters. Bacteria in biofilms are resistant to antimicrobial agents and difficult to treat. Biofilms made up of Staphylococcus epidermidis bacteria are a major cause of infection in hospitals, and can lead to sepsis.
A research team led by Dr. Michael Otto of NIH's National Institute of Allergy and Infectious Diseases (NIAID) set out to determine how bacteria from biofilms detach and disperse. They looked at a protein released by S. epidermidis called phenol-soluble modulin beta, or PSMβ. They chose PSMβ because of its structure, which hinted that it might act like a type of molecule, called a surfactant, that can help bacteria spread. The study was published online on December 6, 2010, in the Journal of Clinical Investigation.
The scientists first confirmed that S. epidermidis in biofilms make PSMβ protein. Then, to test whether the protein promotes biofilm formation, they cultured mutant bacteria that can't make their own PSMβ. They found that adding medium levels of PSMβ to the cultures led to more biofilm formation, but high levels led to less. This suggested that PSMβ may play a dual role, helping biofilms form while also helping bacteria detach from them.
To look at detachment more directly, the researchers genetically engineered bacteria to turn green upon making PSMβ. When examined under a microscope, the bacteria making PSMβ were seen mostly at the outer layers of the biofilm, or detached and floating in fluid. Moreover, a strong green signal usually appeared just before bacteria disappeared from that area. This suggested that bacteria made PSMβ immediately before leaving the biofilm.
To see if PSMβ could help bacteria spread in a living organism, the team put 2 catheters in mice. One catheter had normal S. epidermidis on it. The other had a mutant lacking PSMβ. Within a few days, the normal bacteria spread to the organs and body fluids, but the PSMβ-lacking bacteria barely migrated at all.
In an attempt to stop the bacteria from spreading, the team treated mice with antibodies against PSMβ. The antibodies prevented bacteria from spreading to all the organs except for the lymph nodes, where numbers were significantly reduced.
PSM proteins have also been found in other Staphylococcus species. Although this research is still in its early stages, it opens up new avenues for curbing biofilm-related infections. "This is very important particularly because it links this mechanism of biofilm detachment to spread of infection in vivo," Otto says.
—by Allison Bierly, Ph.D.