Choline Triggers Exacerbations of Chronic Obstructive Pulmonary Disease in Patients Infected with Pseudomonas aeruginosa

Background: Although exacerbations of chronic obstructive pulmonary disease produced by Pseudomonas aeruginosa infections are a major cause of death, the molecular mechanism that produces them is not well known. Here we focused on the energetic basis of dyspnoea, hypercapnia and acidosis symptoms.

Methods and findings: We used an in vivo exacerbation model exposing mice to cigarette smoke and LPS, to mimic emphysema and infections, and choline challenges to trigger exacerbations, that showed 31% increased in the airway resistance for naïve mice and 250% for smoke/LPS treatment. Tissue resistance was increased 32%, in naïve mice, and 169% for smoke/LPS treatment. A decreased tissue elastance, was confirmed by decreased collagen content and increased alveoli chord length. Consequently, the O₂ demanded was 260% greater for smoke/LPS treated mice, to provide the energy required to pump the same volume of air then for naïve mice. The extra CO₂ produced per ml of air pumped caused hypercapnia and acidosis by 4% decrease in pH.In addition, the bacteria grown with choline had a decrease of 67% in phosphate, 23% ATP and 85% phospholipids with an increase of 57% in polyphosphates, 50% carbohydrates, 100% LPS, consuming 45% less energy relative to the bacteria grown with succinate.

Conclusion: choline, released by P. aeruginosa, triggers exacerbation symptoms by increasing lung resistance, O₂ consumption and producing more pCO₂ in blood with dyspnea, hypercapnia and acidosis. The energetic shift of decreased O₂ bacterial demand and increased lung demand benefits the infection, thus restoring the energetic balance on the host will favor P. aeruginosa eradication.