In a new study, researchers found that mannitol co-treatment with the antibiotic tobramycin did not enhance the antibiotic’s bacterial killing effect in a Cystic Fibrosis (CF) model. The research paper, entitled “Mannitol Does Not Enhance Tobramycin Killing of Pseudomonas aeruginosa in a Cystic Fibrosis Model System of Biofilm Formation,” was recently published in PLoS One.
CF is a chronic and life-threatening disease caused by mutations in the CFTR gene, affecting the respiratory and digestive systems. The CFTR protein acts as a chloride channel, transporting chloride ions across cell membranes, leading to the production of mucus essential to lung function and protection of the lining of airways. Mutations in this protein lead to deficient chloride ion transport and consequently the overproduction of extremely thickened and viscous mucus, which results in deficient lung clearance and function and higher risk of recurrent bacterial infections.
One of the primary and more dangerous bacterial strains involved in lung infection of CF patients is Pseudomonas aeruginosa. The bacterial biofilms that are formed in the lining of CF patients’ airways often become resistant to antibiotics, rendering treatment ineffective and leading to the worsening of the disease. This antibiotic tolerance has been explained through several hypotheses, from the physical characteristics of biofilms where barriers of extracellular matrix protect cells to the presence of dormant cells, that are metabolically inactive and therefore don’t respond to the damage cause by antibiotics. Tobramycin is an antibiotic that has been used in maintenance treatment of CF patients with lung infections. It has presented successful results in clearing young patient’s lungs of P. aeruginosa, but in older patients the results have been incomplete. A recent study demonstrated that mannitol had a synergistic effect with tobramycin, making the resistant cells more vulnerable to the antibiotic and arresting biofilm growth.
In order to test this antibacterial activity enhancement by mannitol, researchers at the Geisel School of Medicine at Dartmouth University in collaboration with Novartis Pharmaceutical developed a model where eight strains of P. aeruginosa, five from clinical CF isolates, were grown on the surface of airway cells from a cystic fibrosis patient. This more clinically relevant model included the growth of robust biofilms observed in CF and was compared to non-CF airway cells. Results show that co-treatment of tobramycin with mannitol had no enhancement effect in bacterial effect and did not reduce the bacterial population in the CF airways. The research study illuminates biofilm processes of resistance and confirms the usefulness of this type of model system for pre-clinical research.