College of Medicine Assistant Professor Renee Fleeman continues to refine a powerful therapy for drug-resistant bacteria that pierces the gooey coating that anchors and protects such germs from the drugs we take to kill them.
Her research, backed by a five-year $813,130 National Institute of Allergy and Infectious Diseases grant, found that an antimicrobial peptide naturally found in cows weakens the biofilm defenses of Klebsiella pneumoniae bacteria and destroys it.
Now in their fourth year of research, Fleeman and her lab have discovered exactly how the peptide works in findings published in PLOS Pathogens.
鈥淥ur research is very advantageous for healthcare because about 80% of bacterial infections being treated in the clinic are bacteria living in a biofilm state, which makes them resistant to virtually every antibiotic available,鈥� she says.
The results represent a critical step to potentially applying this peptide as a therapy and eventually treating patients, as the findings show they can and kill biofilm-embedded bacteria in animal models.
Parsing out the Peptide
K. pneumoniae is found in the intestines and is usually harmless, however, the bacterium develops resistance over a person鈥檚 lifetime as they are exposed to antibiotics. The bacteria also can spread from the intestine to other parts of the body in immunocompromised patients and those who have internal ruptures or exposure to contaminated medical devices. That exposure can lead to pneumonia, urinary tract or wound infections.
鈥淲hat happens is the bacteria infects the wound, proliferates, and then invades through the bloodstream where it travels to the liver, kidneys and spleen,鈥� Fleeman says. 鈥淲e found our peptide was able to decrease the bacteria at the source while limiting the bacteria鈥檚 ability to move through the blood.鈥�
Fleeman and her lab鈥檚 most recent study found that the peptide triggers a dual stress response that tricks the bacteria to break out of their protective biofilm.
They discovered the genetics of a specific protein in the bacterium when turned on in the germ causes it to break from its own protective biofilm. The peptide, in effect, damages the protection and then stresses the bacterium into shedding its protection, making the germ more sensitive to antibiotics and the body鈥檚 immune system.
鈥淏y hitting the membrane as well as protein synthesis at the same time, it’s a double punch that triggers a genetic change in the cell to make it think it needs to break out of the biofilm as a response to our peptide,鈥� Fleeman says.
The team says their sustained research aims to demonstrate that their peptide can work synergistically with existing antibiotics. They envision long-term applications could involve a topical cream that weakens the bacteria鈥檚 defenses and allows standard antibiotics to work more effectively.
鈥淲e鈥檙e moving our research forward and we鈥檙e very hopeful,鈥� Fleeman says.
Preparing for the Post-Antibiotic Era
The first author of this new work is Robert Beckman 鈥�23, who graduated from 麻豆映画传媒 with a bachelor鈥檚 degree in health sciences, managed Fleeman鈥檚 lab and is now on his way to the University of Michigan for his Ph.D.
His previous work as an EMT gave him firsthand exposure to infectious diseases and their impact on patients. He says helping to lead the study and working with Fleeman helped prepare him for a career in medical research.
鈥淚 have developed a strong foundation in research and gained insight into the many components that define an effective scientist,鈥� he says. 鈥淢y long-term goal is to remain in academia and eventually lead my own research lab. I plan to continue focusing on bacteriology, with a particular emphasis on pathogenic bacteria and drug discovery applications.鈥�
Funding and Disclosure:
Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R00AI163295. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
