#NACFC2016 – CF Lung Exacerbations Driven by Fermentative Bacteria, Preferring Acidic pH

According to a new study, acute exacerbations of cystic fibrosis (CF) are associated with a surge of bacteria that do not depend on oxygen (called anaerobic or fermentative bacteria), which thrive when mucus becomes more acidic. Antibiotic treatment kills this bacteria, allowing Pseudomonas aeruginosa to thrive, but as the treatment effect wanes, the fermentative bacteria return.

The data was presented today at the 30th Annual North American Cystic Fibrosis Conference (NACFC) Oct. 27-30 in Orlando, Florida, in a session called “Pathogenesis of Airway Infection.”

The presentation was titled “pH and Antibiotic Pressure Drive Anaerobic Fermentation Associated  With Pulmonary Exacerbations.”

Early data indicated that anaerobic bacteria — which, instead of oxygen, uses a fermentative kind of  metabolism — are linked to CF worsening. Robert Quinn, PhD, of the University of California at San Diego, and his research team figured that the pH of mucus could be a driver of processes, enabling such bacteria to thrive.

To test whether this may be the case, the team used a new model of the CF lung called the WinCF microbial culture system. The model aims to mimic the conditions of a CF airway plugged with mucus and allows realistic studies of microorganisms.

The team gathered mucus from 18 patients with CF and six healthy controls, and transferred it to the model system. Researchers varied the pH between 5 and 8.5, and then used RNA sequencing of bacterial genomes to determine how microbes were affected by the changes in pH.

Researchers found that two different bacterial communities were driven by the effects of pH. At a more acidic pH, a community of anaerobic bacteria dominated, while Pseudomonas aeruginosa was the dominant species at a higher pH. Researchers also found that antibiotics disrupted this balance by killing the anaerobic bacteria, while having little effect on Pseudomonas aeruginosa.

In addition to these large effects, the team also noted more subtle consequences of changes in pH, as the metabolites produced by P. aeruginosa were changed with the pH.

Using mathematical modeling, the team confirmed that pH affected the microbial community composition, but the model also suggested that the width of a bronchus may impact the dynamics, as wider bronchi give more room for anaerobic fermentation.

The model also suggested that antibiotics trigger a cycle in which anaerobic bacteria are killed by them giving room to P. aeruginosa, but as antibiotic treatment is stopped, anaerobic species become re-established in the lung.

“This study supports the observation that CF exacerbations are associated with a bloom of fermentative anaerobes at lower mucus pH. Antibiotic pressure destroys anaerobes setting up a cyclic dynamic with P. aeruginosa. This cycling microbial system is likely crucial to CF disease progression and clinical outcomes,” the team wrote in their NACFC abstract.