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Experimental Treatment Proves Effective Against 'Superbugs'

Synthetic peptides inhibit bacterial growth

A treatment developed at the University of Pittsburgh Center for Vaccine Research has been found to be more effective than traditional antibiotics at inhibiting the growth of drug-resistant bacteria, including so-called “superbugs” resistant to almost all existing antibiotics, which plague hospitals and nursing homes, according to findings published in Antimicrobial Agents and Chemotherapy.

“Very few, if any, medical discoveries have had a larger impact on modern medicine than the discovery and development of antibiotics,” said senior author Ronald C. Montelaro, PhD. “However, the success of these medical achievements is being threatened due to increasing frequency of antibiotic resistance. It is critical that we move forward with development of new defenses against the drug-resistant bacteria that threaten the lives of our most vulnerable patients.”

Each year in the U.S., at least 2 million people are infected with drug-resistant bacteria, and at least 23,000 die as a direct result of these infections, according to the Centers for Disease Control and Prevention.

On the tail end of the human immunodeficiency virus (HIV) surface protein, there is a sequence of amino acids that the virus uses to “punch into” and infect cells. Montelaro and his colleagues have developed a synthetic and more efficient version of this sequence –– called engineered cationic antimicrobial peptides (eCAPs) –– that can be chemically synthesized in a laboratory setting.

The team tested two eCAPs against a natural antimicrobial peptide (LL37) and a standard antibiotic (colistin [polymyxin E]). The latter is being used as a last-resort antibiotic against multidrug-resistant bacterial infections. The investigators performed the tests using 100 different bacterial strains isolated from the lungs of pediatric cystic fibrosis patients and 42 bacterial strains isolated from hospitalized adult patients.

LL37 and colistin each inhibited the growth of approximately 50% of the clinical isolates, indicating a high level of bacterial resistance to these drugs. In contrast, the two eCAPS inhibited growth in about 90% of the test bacterial strains.

“We were very impressed with the performance of the eCAPs when compared with some of the best existing drugs, including a natural antimicrobial peptide made by Mother Nature and an antibiotic of last resort,” said Montelaro. “However, we still needed to know how long the eCAPs would be effective before the bacteria develop resistance.”

The team challenged Pseudomonas aeruginosa with both the traditional drugs and eCAPs in the lab. P. aeruginosa is a highly infectious and pathogenic bacterium that flourishes in medical equipment, such as catheters, and causes inflammation, sepsis, and organ failure.

The bacterium developed resistance to the traditional drugs in as little as 3 days. In contrast, it took 25 to 30 days for the same bacterium to develop resistance to the eCAPs. In addition, the eCAPs worked just as effectively at killing P. aeruginosa after the bug became resistant to the traditional drugs.

“We plan to continue developing the eCAPs in the lab and in animal models, with the intention of creating the least-toxic and most effective version possible so we can move them to clinical trials and help patients who have exhausted existing antibiotic options,” Montelaro said.

Source: EurekAlert; December 9, 2014.

 

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