Pseudomonas aeruginosa killed by the engineered cationic antimicrobial peptide (eCAP). Killed bacteria (red), living bacteria (green). Credit: Jeffrey Melvin, Pitt
A potential drug therapy developed at the University of Pittsburgh Center for Vaccine Research (CVR) has proven effective against tough bacterial biofilms and a respiratory virus simultaneously. The drug outperforms traditional therapies in the laboratory setting. “To the best of our knowledge, no other antibiotics out there work on both the bacteria and the virus during a co-infection,” said Jennifer M. Bomberger, Ph.D., assistant professor in Pitt’s Department of Microbiology and Molecular Genetics.
Chronic infections, such as those that kill cystic fibrosis patients, resist the body’s efforts to clear them from the lungs, sinuses or other areas. Often these infections are characterized by biofilms, which are bacteria that stick together forming colonies that are as much as 400X as resistant to antibiotics as a single bacterium.
The potential drug therapy relies on an engineered cationic antimicrobial peptide, or “eCAP,” which is a synthetic and more efficient version of naturally occurring antimicrobial peptides that form a first line of defense against infections in humans. Developed by Ronald C. Montelaro, Ph.D., professor and co-director of Pitt’s CVR, the eCAP works by “punching into” bacteria and viruses, thereby destroying them.
Model of P. aeruginosa-RSV coinfection of bronchial epithelium and treatment with antimicrobial peptides (AMP). P. aeruginosa first attaches to bronchial epithelial cells infected with RSV. These attached bacteria form biofilms on the RSV-infected epithelium. Lack of treatment results in robust biofilm proliferation and release of infectious viral particles in the airway lumen. Treatment with WLBU2 results in disruption of biofilms, reducing both the number of biofilms and the size of the biofilms that remain after 1 h of treatment, and reduction of infectious virus particles in the airway lumen.
Dr. Bomberger and her team tested the eCAP in the laboratory by growing biofilms of drug-resistant Pseudomonas aeruginosa bacteria on the cells that line the airway and then treating them for one hour with the eCAP. The eCAP was 50X more effective at fighting the biofilm than traditional treatment, but did not harm the airway cells. The team then did the same test, this time on airway cells first infected with respiratory syncytial virus (RSV), which causes serious infection in infants and older adults, as well as people with compromised lungs. In February, Dr. Bomberger reported in the journal Proceedings of the National Academy of Sciences that RSV helps Pseudomonas aeruginosa biofilms grow.
“When the body responds to fight the virus, it inadvertently leaves an Achilles heel by fostering an environment rich in the nutrient iron, which aids the bacteria in forming a biofilm,” said Dr. Bomberger.
The eCAP was 10X more effective at fighting the biofilm in a virus-bacteria co-infection compared with traditional therapy. When eCAP was used on airway cells infected only with RSV, the number of viable virus particles was reduced by more than 150X. The eCAP also worked against bacterial biofilms grown on plastic, indicating that it could be a good treatment for cleaning medical equipment, such as bronchoscopes.
“We’re incredibly encouraged by these results,” said Dr. Montelaro. “Again and again, eCAPS are performing well in laboratory tests and mouse models. They’re an exciting possibility to help solve the antimicrobial-resistant superbug crisis that our world increasingly faces.” http://www.eurekalert.org/pub_releases/2016-05/uops-pdw050916.php
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