Bacteria that normally reside in the lungs, not causing disease, produce a compound that makes harmful bacterial infections with Pseudomonas aeruginosa difficult to fight. These infections can be particularly devastating for people with cystic fibrosis (CF), and the scientists hope their discovery will lead to better treatments for P. aeruginosa infections in vulnerable patient groups.
P. aeruginosa is not a threat to healthy people, but in patients with airway disease, the bacteria can cause a persistent infection with severe inflammation of the lung tissue. People with CF have difficulty in clearing mucus and, subsequently, microbes from the airways. Scientists have suspected that interactions between P. aeruginosa and other lung bacteria might contribute to the severity of the infection.
Researchers at Weill Cornell Medicine and Cornell University showed that normal lung bacteria, generally referred to as the microbiome, create a compound called 2,3-butanediol. It is this chemical that makes P. aeruginosa infection more resistant and, generally, worse than would be expected. The study, “The fermentation product 2,3-butanediol alters P. aeruginosa clearance, cytokine response and the lung microbiome,” was published in The ISME Journal.
“It’s always been a big mystery why patients with cystic fibrosis do so poorly once they have P. aeruginosa in the lung. Our findings show that we not only have to look at the bacteria itself, but we also have to look at the interaction of the natural bacteria in the lung,” Dr. Stefan Worgall, distinguished professor of pediatric pulmonology and a professor of pediatrics and genetic medicine at Weill Cornell Medicine, and a senior study co-author, said in a press release:
Studying mice, the research team showed that the animals infected with P. aeruginosa in combination with the bacterial compound (2,3-butanediol) had 100 times more bacteria in their lungs after three days than mice infected only with P. aeruginosa. The dual infected mice also had more inflammatory cytokines in their lungs.
The findings explain not only the severity of this particular infection, but also why bacterial overgrowth with a variety of different bacteria is common in the lungs of CF patients.
For CF patients with P. aeruginosa or other bacterial infections, the standard treatment involves lengthy antibiotic regimens. Such therapies are often far from optimal, and this study may explain why, since it is likely that similar interactions may also exist with other bacterial species.
“We need to understand the disease process better, and how this infection settles in the lung and interacts with the microbiome,” Dr. Largus Angenent, the study’s other senior co-author and a professor of biological and environmental engineering at Cornell. “That understanding is what will eventually lead to new therapies.”
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