By
Doris Wu
April 10, 2007
To battle biofilms of bacteria, gallium, a rare metallic element, can be used to trick bacteria uptake systems to destroy them, UW researchers say.
With antibiotic-resistant bacteria becoming more difficult to eliminate, researchers need to find new ways to help patients overcome long-term and acute illnesses.
“Basically, the problem that we are trying to address is we need new antibiotics,” UW microbiologist Pradeep Singh said. “There is an increasing resistance to antibiotics. … In many chronic, long-lasting persistent infections, current antibiotics don’t work…” he said. “The main reason for that is that in many chronic infections, the bacteria are living in a biofilm.”
Biofilms are clusters of bacteria that live as a community and are encased in a slime-like matrix that consists of polysaccharides (long chains of sugar) and DNA. This slime matrix holds the bacteria together and protects them.
“It’s been long known that tampering with iron availability can inhibit or discourage cells from forming biofilm,” microbiology professor Matthew Parsek said. The UW researchers have teamed up with scientists from the University of Cincinnati and the University of Iowa to attempt to solve this problem by using gallium.
“Because [gallium is] similar in size and valency as iron, it can mimic iron in terms of the biology,” Parsek said.
Iron is needed for the bacteria to grow and form biofilm communities.
“Some of our previous work suggested that if we targeted the ability of bacteria to target iron that it might be a good strategy,” Singh said. “The bacteria are tricked into taking up gallium by their uptake systems. Once it gets inside the bacterial cells, it cannot function the same way as iron, and so it poisons them.”
Another reason for gallium’s effectiveness is its ability to target biofilms.
“Biofilms are difficult to kill with conventional antibiotics … because the bacteria inside those communities are often growing very slowly, and slow growing bacteria are difficult to kill … [but they] are also starved for iron,” Singh said. “So they have revved up their iron uptake systems, [making them] particularly sensitive to gallium. So we’re exploiting the physiology of the bacteria … to kill them.”
Singh and the research team have experimented with gallium in mice to rid them of pseudomonas aeruginosa, bacteria that cause cystic fibrosis, which is the most common lethal genetic disease found in Caucasians.
Pseudomonas aeruginosa also causes severe infections in wounds, burns, medical devices like catheters and immunocompromised people.
“[We] tested against two types of infections in mice. One infection was a chronic lung infection and the other was an acute lethal infection,” Singh said. “We found gallium to be very effective … and were able to prevent death in almost all the mice.”
For the acute infection, they gave the mice a lethal dose of bacteria to their lungs and treated them with a single drop of gallium to the nose.
While the results are hopeful, research is still in the initial stages, and more tests will be conducted before it can be tried in humans.
“The fact that [gallium is] already FDA-approved is very promising,” Parsek said.
Reach reporter Doris Wu at news@thedaily.washington.edu.
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