Researchers Develop Novel Antimicrobial Peptides To Combat ‘Superbugs'

Researchers at the University of Pittsburgh’s Center for Vaccine Research (CVR) have developed a set of novel antimicrobial peptides that are more effective than traditional antibiotics at fighting different drug-resistant bacteria, including the notorious "superbugs".

"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, Ph.D., professor and co-director of the CVR. "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."

To develop these novel anti-infectives, Dr. Montelaro and his team looked at the HIV surface protein, which has a sequence of amino acids at its tail end that it uses to infect cells. The researchers created an improved, synthetic version of this sequence, called engineered cationic antimicrobial peptides, or "eCAPs".

The team then evaluated two of these antimicrobial peptides or eCAPs against 100 different bacterial strains isolated from the lungs of hospitalized pediatric cystic fibrosis patients and 42 bacterial strains isolated from hospitalized adult patients. The eCAPs were tested in comparison with a natural antimicrobial peptide (LL37) and a standard antibiotic (colistin), which is considered a last-resort antibiotic against multidrug resistant bacterial infections.

The two eCAPS were found to inhibit bacterial growth in about 90 percent of the test bacterial strains, while the other two well-known antibiotics each inhibited growth of only about 50 percent of the bacteria.

"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 Dr. Montelaro. "However, we still needed to know how long the eCAPs would be effective before the bacteria develop resistance."

The researchers also tested the resistance of bacteria towards the eCAPs in comparison with the traditional drugs, by using a highly infectious bacterium found in hospitals that causes inflammation, sepsis, and organ failure. While the bacterium developed resistance to the traditional drugs within just 3 days, it took almost 30 days for the same bacterium to develop resistance to the eCAPs.

The researchers now intend to develop the eCAPs further in the lab and in animal models so that they can create the least-toxic and most effective versions possible, which will then be moved to clinical trials and help patients who have exhausted existing antibiotic options.

There are more than 2 million people infected with drug-resistant bacteria every year in the U.S., with over 23,000 deaths due to these infections, the researchers say.

The study was published online in the journal Antimicrobial Agents and Chemotherapy.