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  Biofilms Explore this link to learn about biofilms and MSU–Center for Biofilm Engineering research.

Bacteria thrive on 'film'

This slimy glue is everywhere -- in your body, on your teeth -- and hard to kill
By Chris Emery
Sun reporter
Originally published March 23, 2007
When he was studying for his doctorate in microbiology, Mark E. Shirtliff thought 
he knew a lot about bacteria.

Then things got scary.

He discovered that bacteria can band together into sheets - called biofilms. 
When they do, they alter their behavior. They build complex communities, establish 
lines of communication and coordinate their actions. Like ants, the
microbes find power in numbers. And they're nasty.

"Infections that should respond to antibiotics don't," Shirtliff said. 
"They become 50 to 500 times more resistant."

With drugs often useless against biofilms in the human body, Shirtliff is trying 
to turn the tables on the slippery infections.

The assistant professor at the University of Maryland Dental School received $1.25 
million this month from the National Institutes of Health for research into vaccines 
that might prevent the deadly films from forming in the first place.

Although the public rarely hears it in popular discussions of health issues, the 
term "biofilm" was coined in a 1978 Scientific American article by William Costerton, 
now of the University of Southern California Dental School. He used it
to describe microbes that clump together on wet surfaces.

"It came up in dentistry first," Costerton said. "They called it plaque. I just 
proposed [that] the biofilm isn't just in the mouth, but everywhere."

In fact, biofilms are just about everywhere. They coat everything from Alpine river 
rocks to neglected teeth. Every year they cause billions of dollars of damage to ship 
hulls, oil pipelines and machinery by corroding metal surfaces and
clogging up the works.

These plaques often contain a variety of microorganisms, including bacteria, protozoa 
and algae suspended in slimy glue called polysaccharide that holds them together and 
binds them to surfaces. When enough of the organisms have collected,
they undergo metabolic changes that make them better team players.

"We tend to think of them as primitive single-celled organisms," said Phil Stewart, 
the director of the Center for Biofilm Engineering at Montana State University. 
"But there is a lot of cooperation and coordination comparable to something more
like an ant colony. It allows them to accomplish more than they could on their own."

Particularly vexing is the ability of virulent bacterial infections to resist attack 
after forming a biofilm. "We could pump bleach into your system," Shirtliff said, 
"and it probably wouldn't do anything."

That's saying something. Chlorine bleach is the microbiologist's ultimate weapon
- it's used to disinfect the labs that house the world's most dangerous germs.

Like soldiers hiding in a castle, the bacteria inside the film are protected from 
drugs design to kill them. The cells are also starved for nutrients. This makes 
them grow and divide slowly - providing even more drug resistance, since
antibiotics often target fast-growing cells.

The stress also puts biofilm bacteria on the defensive, causing them to release 
caustic acids and proteins. "They start freaking out," Shirtliff said. "They turn
 on stress response genes that make them attack the antibiotic."

Compounding the problem, the stress response tricks the natural immune system into 
using the wrong attack plan. When the macrophages and other white blood cells that 
form the body's police force arrive on the scene, they're ambushed and
destroyed by the biofilm's arsenal of proteins and acids.

Biofilm infections often return because antibiotics kill only the free-floating - 
or planktonic - bacteria. When a patient stops taking the drug, new free-roaming 
bacteria emerge from the biofilm and the infection spreads again.

Scientists estimate that 65 percent to 80 percent of chronic infections in 
industrialized nations linger on because of biofilm formation. Biofilms appear in 
patients with cystic fibrosis, gum disease and chronic inner ear, urinary tract and
bone infections.

Medical devices such dental implants, catheters, artificial joints and heart valves
are vulnerable to biofilm formation.

Central venous catheters, a type inserted into most intensive-care patients in 
hospitals, are a common source of bacterial biofilms. About 80,000 of ICU patients 
contract bacterial infections from the catheters each year - and about 35 percent
of those die from the infection, according to the Centers for Disease Control 
and Prevention.

When biofilms grow on bone and metal after joint replacement surgery, the only 
option may be to start again from scratch.

"The only way you can get it out of there is by carving it out," Shirtliff said. 
"If an artificial knee gets infected, you're going to have to take that knee out 
and put another one in."

In his research, Shirtliff has focused on one particularly bad actor that has 
gotten a lot of press lately: methicillin resistant staphylococcus aureus (MRSA). 
The antibiotic-resistant bacteria kill about 90,000 people in the United States
every year, according to the CDC.

Because MRSA infections are difficult or impossible to eradicate once a biofilm 
is fully formed, Shirtliff is searching for a way prevent the films from growing.

The trick, he believes, is to hone in on the odd behavior of the biofilm bacteria. 
He has identified proteins the bacteria produce in abundance as they form a film 
and hopes to develop antibodies that will target those proteins.

Like an army attacking a half-built fortress, the antibodies would attack the 
immature biofilm and destroy it before its defenses are fully formed.

"The antibodies come in and deactivate the proteins and can destroy the biofilm," 
he said. "The immune cells could also come in safely then and attack as well."

To test his theories, Shirtliff grows MRSA biofilms in silicon tubing in his lab 
at the dental school and looks for protein targets.

Anti-biofilm vaccines he has developed have proven effective for treating rabbits 
with MRSA bone infections. He hopes to move on to clinical trials in humans within 
four years, he said.

He said a vaccine might be the best way to combat MRSA because the bacteria are so 
widespread. "Here in the United States," he said, "it's hard to cork that bottle."
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