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Pitt study may offer way to fight superbugs

| Thursday, Dec. 11, 2014, 12:22 a.m.

Small proteins designed to drill into bacteria could be used to treat extremely drug-resistant superbugs, according to a recent study that University of Pittsburgh scientists published.

The small proteins, or peptides, could help in the fight against hospital-acquired infections that don't respond to antibiotics and that sometimes find their way into the general population, said lead scientist Ronald Montelaro of the Pitt Center for Vaccine Research.

“Bacteria are very clever,” said Montelaro, referring to their ability to quickly become resistant to drugs. “There's been an increased urgency to create novel classes of antibiotics.”

Hospital-acquired infections are a major health care cost. A 2013 study published by Harvard Medical School found that the most common hospital-acquired infections cost the United States about $10 billion per year. But with increasing antibiotic-resistance and few new antibiotic chemicals being developed, researchers have turned to studying, and now mimicking, naturally occurring bacteria-busting peptides found in everything from frogs to people, Montelaro said.

Showing results

In the study, published online on Nov. 24 in Antimicrobial Agents and Chemotherapy, Montelaro and colleagues engineered two simple peptides that twist into tight helices and insert themselves into the cell membranes of bacteria. They tested the molecules against both a naturally occurring one found in human lungs that doesn't twist as tightly and a drug of last resort in hospital infections. Their goal was to see how well they would kill highly drug-resistant bacterial cultures from 142 children and adults with lung infections.

They found that both the engineered peptides killed around 90 percent of bacteria grown from the drug-resistant cultures, whereas the natural peptide and the drug of last resort killed anywhere from 13 to 63 percent of bacteria, depending on the biochemistry of the cell membrane.

“It's much like a pin bursting a balloon,” said Montelaro.

Finding promise

Furthermore, when they took one particularly difficult-to-kill bacterial species found in hospitals, called Pseudomonas aeruginosa, they found that it took almost one month for the otherwise smart bugs to figure out how to become resistant to the engineered peptide. For the naturally occurring peptide and the drug-of-last-resort, the bugs were resistant by two weeks.

The mechanism by which the engineered peptides outdo the other test molecules isn't clear, but it may have something to do with the tight helix and the way chemical charges align, said Montelaro. The next step is to study the peptides in animal models.

The research is promising, and it's possible that the peptides can be used in combination with antibiotics and other antimicrobial agents, said Robert Ernst of the University of Maryland School of Dentistry, who was not involved in this research but is a collaborator of Montelaro's.

“There's no silver bullet. I think we're moving to the stage where a single antibiotic isn't enough. We're running out of natural antibiotics,” Ernst said.

Megha Satyanarayana is a staff writer at Trib Total Media. She can be reached at 412-320-7991 or megha@tribweb.com.

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