MORGANTOWN, WV (LOOTPRESS) – West Virginia University microbiologists have identified an antibody capable of killing one of the most drug-resistant bacteria, Pseudomonas aeruginosa.
Now, they are investigating whether it can be combined with existing antibiotics to create an effective treatment against infections.
[irp posts=”133625″]
The bacterium causes a range of diseases, including sepsis and pneumonia, as well as chronic infections affecting the skin, eyes, and lungs.
“This pathogen is becoming extremely highly resistant to antibiotics. There are even strains of P. aeruginosa that are resistant to all antibiotics available right now,” said Mariette Barbier, associate professor and chair of the Department of Microbiology, Immunology and Cell Biology at the WVU School of Medicine.
“These problems make the treatment of P. aeruginosa infections particularly challenging.”
The infections typically occur in healthcare settings and spread through contaminated surfaces, medical equipment, or direct person-to-person contact.
Those most at risk include immunocompromised individuals, recent surgery patients, and people with cystic fibrosis, who frequently experience recurring P. aeruginosa infections.
Barbier and her team initially sought to develop a vaccine to prevent infection but shifted their focus to the potential use of immune system antibodies in drug development.
“Our immune system makes really good antibodies that will clear the pathogen,” she said.
“We want to know if we can use the immune system to our advantage. Instead of vaccinating people, we wonder if there is a way we can harvest those antibodies and use those as drugs for the treatment of infections.”
Typically, antibodies signal the immune system to eliminate bacteria, but researchers discovered a unique antibody produced by mice that acts independently.
“It actually kills the bacteria itself,” Barbier said.
“If you just take the antibody and the bacteria and put them in a test tube, the bacteria die. That’s not something we knew antibodies could do and that has really opened our eyes in terms of the potential of antibodies as therapeutics.”
The researchers immunized mice with P. aeruginosa, prompting their immune systems to generate antibodies.
They then isolated B cells responsible for antibody production and developed methods to produce them for drug testing.
The antibody that demonstrated success is called WVDC-0496, named after the West Virginia Vaccine Development Center.
Barbier’s team is now studying how it destroys bacteria and whether it could serve as a therapeutic.
The five-year study is funded by a $3.5 million grant from the National Institute of Allergy and Infectious Diseases.
Working alongside Barbier are Heath Damron, associate professor and director of the Vaccine Development Center; Emel Sen Kilic, a former WVU research assistant professor; and Spencer Dublin, a second-year doctoral student in biomedical sciences.
Additional students will be recruited for the project.
The research builds on discoveries made over the past 15 years. As a doctoral student, Damron identified ways to grow P. aeruginosa under stress conditions that mimic its behavior in the lungs of cystic fibrosis patients.
He and Barbier later studied these growth conditions, and in the past three years, Dr. Jason Kang, a School of Medicine alumnus, isolated antibodies capable of directly killing bacteria.
“We know that if this antibody is administered to mice, it can prevent them from dying of sepsis or pneumonia,” Barbier said. “What we don’t know is whether it could be used in combination with antibiotics or whether it would work against those strains that are extremely resistant to antibiotics.”
Dublin, a first-generation college student from Fairmont, is assisting in testing how the antibody interacts with different antibiotics.
“We actually have observed synergy between our antibody and select antibiotics that increase their function at even lower concentrations,” he said.
Dublin will also mentor other students who join the lab.
Barbier will collaborate with researchers from the University of Texas to determine whether the antibody can destroy P. aeruginosa in biofilms—bacterial clusters encased in a protective barrier that makes them difficult to treat.
“For example, P. aeruginosa causes biofilms in catheters and that’s a reason why some people develop bloodstream infections,” Barbier said. “Once biofilms form, they are very difficult to treat. We want to know if our antibodies can tackle this particularly challenging problem.”
Beyond WVDC-0496, Barbier hopes the study will lead to the development of additional antibodies with similar functions to combat other multidrug-resistant bacteria.
