MORGANTOWN — About half of all people with cystic fibrosis, the most common genetic disorder in the U.S., die from a lung disease before they turn 40, according to WVU.
A form of pneumonia called Pseudomonas aeruginosa is a likely culprit. These bacteria have become so hard to treat, the Centers for Disease Control and Prevention deem it a serious threat to the nation, according to a press release from the WVU School of Medicine.
“That’s the main reason I work with Pseudomonas,” said Mariette Barbier, an assistant professor in the university’s School of Medicine. “It is on the CDC’s list of antibiotic-resistant bacteria
of concern.”
Barbier and her research team are investigating ways to keep cystic fibrosis patients and other at-risk populations — such as patients hospitalized for severe burns or recovering from major surgery — from catching the deadly illness.
The Cystic Fibrosis Foundation, National Institutes of Health and West Virginia Higher Education Policy Commission are funding her work, the release states.
Pseudomonas’ versatility is one reason antibiotics have a hard time conquering it. It’s especially good at adapting to new and changing environments, the release states. If just one Pseudomonas cell survives antibiotics, it can multiply into even more cells that are impervious to the treatment.
“I tell my students that mutations are rare, but mutants are common,” said Barbier, who teaches in the WVU Department of Microbiology, Immunology and Cell Biology. “Pseudomonas has acquired throughout its evolution numerous intrinsic mechanisms of resistance, making it naturally resistant to a large number of antibiotics. And that’s just the baseline.”
Barbier focused her research on preventing infections, not just treating them. In a recent study, she and her colleagues examined what molecular-level resources the bacteria relied on to infect a preclinical model. The goal is a Pseudomonas vaccine to block the bacteria’s access to a crucial resource and prevent infection.
Barbier collected samples of the bacteria during an infection’s early stages. Then sequenced the bacteria’s RNA — the chemical messenger that tells cells what proteins they should build, based on the cell’s ever-changing needs.
“If you sequence the genome, you get everything single thing that it could do,” Barbier explained, “but if you sequence the RNA, you get an idea of what the cells are doing right now.”
Barbier suspected an RNA snapshot would give her an idea of the “weaponry” the bacteria and host were using against each other. She was right. When the bacteria and host were locked in battle, the RNA of both the bacteria and the host instructed cells to crank out a protein tied to iron acquisition. Each side seemed desperate to gobble up as much iron as possible, according to the release.
“It was known for a really long time that iron was essential for humans and bacteria, but seeing it in that way — that interplay of all those proteins just trying to get ahold of it in the model — was unique,” Barbier said.
So she and her team devised a way for a synthesized molecule to reliably trigger an immune-system response. The researchers suspected the models’ immune system would recognize the molecule as foreign, identify the pieces of the bacteria’s protein and use that information to isolate and destroy the actual bacteria when it appeared.
It worked — host’s immune system killed off 99.9 percent of the bacteria.
“I think that this 99.9 percent is great,” Barbier said, “but there still are a lot of bacteria in there. We hope to even further improve that efficacy.”
“There is a great need for a vaccine to prevent [Pseudomonas] infection in cystic fibrosis patients to extend their lives. Dr. Barbier has identified an Achilles’ heel of the pathogen, which can be used to educate the immune system to clear the organism,” said Heath Damron, who directs the center.
Barbier and her team are now investigating what types of immune cell — T cells, B cells or macrophages, for example — are key to that protection. By knowing what aspect of the immune response plays the biggest role in spotting and attacking the bacteria, researchers can fine-tune a vaccine.
She and her colleagues are also exploring vaccines that target multiple proteins at the same time. “Pseudomonas adapts,” Barbier Pseudomonas. “So, if you hit it with one
thing, it’s just going to laugh at you, and it’s going to be annoyed for a little bit, and then it’s going to say, ‘You know what?
I’ll find another way.’ We want to make a multivalent vaccine to provide a broader protection — something that bacteria cannot evolve around.”
