University of Central Florida College of Medicine researcher Renee Fleeman is on a mission to kill drug-resistant bacteria, and her latest study has identified a therapy that can penetrate the slime that such infections use to protect themselves from antibiotics .
In a study recently published in Cellular Reports Physical Sciencese, Fleeman demonstrated that an antimicrobial peptide from cows has the potential to treat incurable infections caused by the bacteria Klebsiella pneumoniae. The bacteria, commonly found in the intestines, are usually harmless. It becomes a health hazard when it enters other parts of the body and can cause pneumonia, urinary tract and wound infections. Those most at risk include older people and patients with other health problems such as diabetes, cancer, kidney failure and liver disease. However, younger adults and people without additional health problems can get urinary tract and wound infections from bacteria that cannot be treated with currently available antibiotics.
The CDC reports that antibiotic-resistant bacteria are a growing threat to global health. A 2019 study found that nearly 5 million people died that year worldwide from drug-resistant infections. A large portion of these deaths are attributable to K. pneumoniae because It has a 50% mortality rate without antibiotic therapy.
These bacteria are most resistant to drugs when they live in a biofilm: microorganisms that stick to each other and are embedded in a protective slime. Recent studies have shown that between 60% and 80% of infections are associated with bacterial biofilms, which increase their resistance to drugs.
“It’s like a layer that the bacteria put around themselves,” says Fleeman.
His research examines ways to remove the protective layer and expose the bacteria so they can be killed by the body’s immune system or by antibiotics that currently cannot pass through the biofilm. Through that research, Fleeman discovered how peptides made by cows can quickly kill K. pneumonia.
She determined that the peptides interact with sugar bonds that keep the slime intact. She compared the process to cutting a chain link fence. Once multiple chains are cut, the integrity of the slime structure is damaged and the peptide can enter and destroy bacteria that are no longer protected.
“Our research has shown that the peptide polyproline can penetrate and begin to break down the slime barrier as early as one hour after treatment,” says Fleeman.
The peptide has another advantage: Once it passes through the slime’s protective barrier, tests showed that it kills bacteria better than antibiotics used as a last resort to treat incurable infections. Peptides kill bacteria by punching holes in their cell membrane, causing death quickly compared to other antibiotics that inhibit growth from inside the cell.
The peptide could also be used as a topical treatment for a wide range of uses, especially for the military, to treat open wounds in the field. “Bacteria divide every 30 minutes, so you have to act quickly,” says Fleeman.
The next phase of their research will seek to understand the biology behind the peptide’s effectiveness and whether combinations of other drugs would help in its application.
His research is funded through a three-year Pathway to Independence R00 grant from the National Institutes of Health and is in its second year. Her study initially began as a K99 award at the University of Texas at Austin, where she worked before joining UCF in September 2022.
Fleeman says research into resistant infections must continue because they pose a major health threat.
“It is estimated that by 2050, antibiotic-resistant bacterial infections will be the leading cause of human death,” he says. “Our work is focused on preparing for this post-antibiotic era battle, where the common antibiotics we take for granted will no longer be effective, jeopardizing cancer therapy, organ transplants and any modern medical advances that depend on effective antibiotic therapies.