Mannitol Does Not Enhance Tobramycin Killing of Pseudomonas aeruginosa in a Cystic Fibrosis Model System of Biofilm Formation.
Cystic Fibrosis (CF) is a human genetic disease that results in the accumulation of thick, sticky mucus in the airways, which results in chronic, life-long bacterial biofilm infections that are difficult to clear with antibiotics. Pseudomonas aeruginosa lung infection is correlated with worsening lung disease and P. aeruginosa transitions to an antibiotic tolerant state during chronic infections. Tobramycin is an aminoglycoside currently used to combat lung infections in individuals with CF. While tobramycin is effective at eradicating P. aeruginosa in the airways of young patients, it is unable to completely clear the chronic P. aeruginosa infections in older patients. A recent report showed that co-addition of tobramycin and mannitol enhanced killing of P. aeruginosa grown in vitro as a biofilm on an abiotic surface. Here we employed a model system of bacterial biofilms formed on the surface of CF-derived airway cells to determine if mannitol would enhance the antibacterial activity of tobramycin against P. aeruginosa grown on a more clinically relevant surface. Using this model system, which allows the growth of robust biofilms with high-level antibiotic tolerance analogous to in vivo biofilms, we were unable to find evidence for enhanced antibacterial activity of tobramycin with the addition of mannitol, supporting the observation that this type of co-treatment failed to reduce the P. aeruginosa bacterial load in a clinical setting.
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Katherine E
KE
Price
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Giulia
G
Orazi
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Kathryn L
KL
Ruoff
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
Wesley P
WP
Hebert
Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States of America.
George A
GA
O'Toole
Novartis Pharmaceutical Corporation, East Hanover, New Jersey, United States of America.
Paul
P
Mastoridis
D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008353:Mannitol / Q000008:administration & dosage; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D014031:Tobramycin / Q000008:administration & dosage
D008353:Mannitol; D014031:Tobramycin