Researchers at the University of Pittsburgh Center for Vaccine Research (CVR) have developed an engineered antimicrobial peptide effective against co-infection by bacterial microfilm and a virus, and as such is a possible new therapeutic agent against chronic and antibiotic-resistant infections. Importantly, the potential drug was tested against Pseudomonas aeruginosa, one of the primary and more dangerous bacterial strains causing lung infections in cystic fibrosis patients.
The article, “Simultaneous Antibiofilm and Antiviral Activities of an Engineered Antimicrobial Peptide during Virus-Bacterium Coinfection,” was published in the journal mSphere.
CF is a chronic and life-threatening disease caused by mutations in the CFTR gene, affecting the respiratory and digestive systems. The mutations lead to deficient chloride ion transport, and consequently the overproduction of extremely thick and viscous mucus, leading to poor lung clearance and function, and a higher risk for recurrent bacterial infections. The bacterial biofilms that form in the lining of CF patients’ airways often become resistant to antibiotics, rendering treatment ineffective.
The opportunistic gram-negative bacterium Pseudomonas aeruginosa is the major pathogen that affects the lungs of CF patients, often leading to chronic infection in those with compromised immune systems.
In previous studies, researchers showed that co-infection with virus promotes biofilm growth and increases bacterial drug-resistance, a growing concern in the medical community as some bacteria are now resistant to almost all existing antibiotics.
Researchers developed an engineered cationic antimicrobial peptide, or “eCAP,” which is basically a more efficient and synthetic version of naturally occurring antimicrobial peptides that are part of the human immune system defense.
Scientists tested these eCAPs in laboratory-grown biofilms of P. aeruginosa on cells that line the airways. One-hour treatment showed that eCAP is 50 times more effective at fighting these drug-resistant biofilms than conventional therapy, while not harming airway cells. Moreover, the researchers tested the molecules on airway cells first infected with the respiratory syncytial virus (RSV), known to cause serious infections and to help bacterial biofilm growth. Results here found that eCAP was 10 times more effective at fighting the biofilm in a virus-bacteria co-infection, and when used on airway cells infected only with RSV, it reduced the number of viable cells by more than 150-fold.
“This is really unusual. To the best of our knowledge, no other antibiotics out there work on both the bacteria and the virus during a co-infection,” the study’s senior author, Dr. Jennifer M. Bomberger, an assistant professor in Pitt’s Department of Microbiology and Molecular Genetics, said in a news release. “Antibiotic-resistant chronic infections are an urgent public health threat, and the development of new therapies has been painfully slow. So to see something work on a virus and the incredibly resistant biofilms that bacteria form is very exciting.”
“We’re incredibly encouraged by these results,” Dr. Ronald C. Montelaro, a study co-author, added. “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.”
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