Bacteria Seen to Work Together to Promote Inflammation in CF

The abundant mucus in the lungs of cystic fibrosis (CF) patients helps certain types of bacteria, called anaerobes, to survive and, in turn, support the survival and proliferation of more dangerous opportunistic pathogens like Pseudomonas aeruginosa, which otherwise would not find the nutrients they need in mucus-lined airways, a study reported. This symbiotic relationship appears to underlie the inflammation that characterizes the disease.

Abnormal mucus in CF lungs allows hundreds of different types of bacteria to grow, but nutrients present in the mucus are not sufficient to support the survival of many other types bacteria. As such, the question as to how these bacteria obtain necessary nutrients has puzzled scientists for quite some time.

The study suggests that, although certain bacterial species cannot use lung mucus as a viable substrate, other types find mucins, the major constituent of mucus, a large and rich pool of essential nutrients like amino acids (nitrogen) and sugars (carbon). The study, by Jeffrey Flynn, PhD, and colleagues from the University of Minnesota, is titled “Evidence and Role for Bacterial Mucin Degradation in Cystic Fibrosis Airway Disease,” and published in PLoS Pathogens.

Researchers recruited 48 patients from the University of Minnesota Adult CF Center with the ability to expectorate, or cough up,  mucus. The sputum was used to culture bacteria populations and to test each species in different nutritional conditions, alone or in co-culture with other sputum bacteria, in order to observe whether they could survive on mucins.

The initial objective was to investigate the nutritional role of mucins in the growth of Pseudomonas aeruginosa, a common bacterial species of lung infections in CF patients. But they observed that P. aeruginosa was not able to use mucins efficiently, which raised the question: What made it possible for these bacteria to survive? Could they be getting help from other bacteria? According to the results obtained, the answer is a clear yes.

“We reveal that a subset of CF microbiota is capable of fermenting mucins for carbon and energy which, in-turn, can support the carbon demands of other respiratory pathogens in co-culture,” the researchers wrote. Fermentation is the process through which bacteria produce molecules for their maintenance in environments of low oxygen, such as what occurs in the lower respiratory tract (trachea, bronchi and lungs). These low-oxygen bacteria are called anaerobic, or anaerobes.

Consistent with these findings, researchers also observed that products indicative of mucin fermentation were abundant in CF patient sputum, and that P. aeruginosa expressed several genes needed to use these products. Together, the observations support the potential role of fermentative metabolic reactions in the development of CF lung disease.

The researchers proposed that, whereas in healthy people anaerobes present in the lower respiratory tract are routinely cleared by the body’s innate defenses, in CF patients, accumulated mucus and defective immune responses allow anaerobes to become established as mucin-fermenting colonies. These colonies provide the nutritional support necessary for the survival of opportunistic pathogens that cannot use mucins themselves, such as P. aeruginosa and Staphylococcus aureus.

These results suggest that the nutritional dynamics among bacteria contributes to the development of CF lung disease, and may be of importance to other airway diseases as well, such as chronic obstructive pulmonary disease (COPD), sinusitis, and ventilator-associated pneumonias. This finding may also help in the design of new therapeutic strategies for the management of disease progression.