P. aeruginosa Variants Contribute to Increased Local Lung Inflammation in CF Patients, Study Reveals

Alberto Molano Ph.D avatar

by Alberto Molano Ph.D |

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Specific Pseudomonas aeruginosa bacteria called mucoid variants, which are linked to poor prognosis of patients with cystic fibrosis (CF), are associated with significantly greater regional lung inflammation, a study has found.

The study, “Mucoid Pseudomonas aeruginosa and Regional Inflammation in the Cystic Fibrosis Lung,” was published in the Journal of Cystic Fibrosis.

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) gene in CF patients causes accumulation of thick and sticky mucus in the lungs, clogging the airways and facilitating infections by opportunistic bacteria like P. aeruginosa.

When P. aeruginosa first colonize the lungs of CF patients, they show a non-mucoid colony appearance in lab cultures, but as the disease progresses the bacteria often mutate into mucoid variants that form thick, stringy, and wet colonies.

Mucoid variants tend to be more resistant to the effects of antibiotics and to be more difficult to be cleared by the immune system. Scientists also have found that mucoid and non-mucoid variants can collaborate to become more resistant to elimination mechanisms.

CF commonly induces more damage to the upper pulmonary lobes. That’s why researchers from The Ohio State University decided to investigate whether preferential upper lobe localization of certain P. aeruginosa variants could contribute to this.

They collected bronchoalveolar lavage (BAL) fluid from the different lobes of the right and left lungs of 14 patients with CF (70% male, median age 23 years).

BAL samples were cultured on agar plates in the lab and the total number of bacteria, as well as the number of mucoid, non-mucoid and mixed P. aeruginosa colonies that grew were counted.

Researchers also assessed the intensity of the inflammatory response in patients’ lungs by measuring the levels of pro-inflammatory cytokines — such as IL-1beta, TNF-alpha, IL-6 and IL-8 — in BAL samples.

They found that P. aeruginosa mucoid and non-mucoid variants were distributed similarly throughout the CF lung lobes. In other words, they could not detect preferential upper lobe localization of specific bacterial variants. In addition, the upper and lower lobes of the CF lung did not exhibit significant differences in the amount of pro-inflammatory proteins.

Still, they found that infections caused by mucoid variants, whether alone or in mixed-variant populations, were associated with significantly higher levels of pro-inflammatory signaling proteins compared to BAL samples that were negative for P. aeruginosa or contained non-mucoid P. aeruginosa variants only.

Thus, P. aeruginosa mucoid colony variants seemed to be promoting inflammation independently of their localization within the lungs.

Although the study had some limitations, including the small number of CF patients enrolled, the team believes these findings “add further insight to a large body of clinical literature demonstrating deleterious impacts of mucoid conversion upon CF patients.”

This suggests that “therapeutics specifically targeting mucoid P. aeruginosa strains” may be beneficial for CF patients.