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In the Works

New ways to fight bacteria

As bacteria develop resistance to antibiotics, researchers look for weapons in viruses, pharmabiotics, frog skins, cockroach brains, the human immune system and disarming compounds.

September 27, 2010|By Amber Dance, Special to the Los Angeles Times

Doctors and infectious bacteria are locked in an arms race. In this ever-escalating battle, the bacteria evolve ways to avoid every drug humans throw at them.

The conflict has intensified lately as more and more bacteria — particularly those lurking in hospitals — become able to resist nearly every antibiotic in our arsenal.

"We throw thousands and thousands of antibiotics on bacteria," says Marcin Filutowicz, a microbiologist at the University of Wisconsin in Madison. "This is tremendous selection for antibiotic-resistant bacteria."

The situation is forcing scientists to think creatively about where the next antibacterial medications will come from and how they will work. Here are five provocative ideas.

Viruses

Humans aren't the only ones who suffer infections. Bacteria, too, can get infected by viruses — and the enemies of our bacterial enemies are, naturally, our friends. These viruses, called bacteriophages or simply phages, are harmless to people but deadly to bacteria.

Scientists first discovered phages in 1917. But when scientists figured out how to make and use penicillin in 1941, Western doctors dropped phage treatments.

On the other side of the Iron Curtain, however, phage therapies remained popular, says Alexander Sulakvelidze, a microbiologist who grew up in what is now the nation of Georgia.

"Almost everyone that I know in Georgia has taken phages at one time or another," Sulakvelidze says. He is the chief scientist at Intralytix Inc., a Baltimore-based company he founded to exploit phages for human benefit.

In recent years, Western scientists have rekindled their interest in phage treatments, and their experiments show the viruses cure bacterial infections in animals. In a 2009 study, published in the Journal of Wound Care, researchers at the Southwest Regional Wound Care Center in Lubbock, Texas, confirmed the safety of Intralytix's viruses on 42 people with chronic leg ulcers.

Since 2006, a few food processing companies have enlisted phages to prevent contamination in their facilities. Intralytix's ListShield infects and kills Listeria monocytogenes, a bacterium that can cause deadly cases of food poisoning.

"The beauty of this is that it's 100% natural, it's not corrosive, it's not harsh," Sulakvelidze says. If you wanted to, "you could drink it."

It should be difficult for bacteria to evade phages by evolving resistance. "The phages, being biological entities, really will evolve along with the infection," says Roy Sleator, a microbiologist at the Cork Institute of Technology in Ireland.

Pharmabiotics

Not all bacteria are bad. A person normally carries around more than four pounds of bacteria that not only don't cause disease, but also help prevent it by taking up space and resources.

Scientists are trying to harness these friendly bacteria to fight off their disease-causing brethren that do manage to get a foothold. This approach is based on the "probiotics" in the yogurts and other products at the grocery store, but Sleator is taking it to the next level by improving those probiotics in the lab. He calls these souped-up microbes "pharmabiotics."

Sleator has created bacteria that are better able to colonize the gut, where they fight listeria infection. In a 2008 study in the journal BMC Microbiology, Sleator reported that mice that ate the supercharged pharmabiotics before swallowing listeria had fewer listeria bacteria in their bodies than mice that ate regular probiotics.

Next, Sleator would like to make his pharmabiotics produce drugs that attack the bad bacteria directly — either by poking holes in their cell walls or neutralizing the toxins they produce. He is also working to ensure that the engineered bacteria could not run rampant in the world at large.

"If they ever find themselves out in the external environment, outside of a treatment setting, they cannot survive," he says.

But inside the body, pharmabiotics can, like phage, evolve in step with disease-causing bacteria, so it should be hard for the bad bacteria to dodge the treatment.

Filutowicz, too, is toying with good bacteria that can seek out the nasty ones and either pump them full of antibiotics or force them to produce the antibiotics themselves. He founded a company, ConjuGon Inc., to develop his ideas. In a 2007 paper in the Journal of Burn Care & Research, Filutowicz reported that his pharmabiotics successfully knocked down infection and promoted survival in mice with infected burns.

Weird places

Many current antibiotics come from bacteria or fungi that need to fight off neighboring microbes. Now, scientists are casting a wider net in their search for new antimicrobial agents — including looking in animals, such as frogs, that are very good at fighting off bacteria.

Michael Conlon, a chemist at the United Arab Emirates University in Al-Ain, invites colleagues to send him samples of the chemicals frogs secrete on their skin so he can test their antibacterial activity.

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