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Human airway mucus alters susceptibility of Pseudomonas aeruginosa biofilms to tobramycin, but not colistin.
Müller, Laura Murgia, Xabier Siebenbürger, Lorenz Börger, Carsten Schwarzkopf, Konrad Sewald, Katherina Häussler, Susanne Braun, Armin Lehr, Claus-Michael Hittinger, Marius
Müller, Laura
Murgia, Xabier
Siebenbürger, Lorenz
Börger, Carsten
Schwarzkopf, Konrad
Sewald, Katherina
Häussler, Susanne
Braun, Armin
Lehr, Claus-Michael
Hittinger, Marius
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Abstract
Objectives: In the context of cystic fibrosis, Pseudomonas aeruginosa biofilms often develop in the vicinity of airway mucus, which acts as a protective physical barrier to inhaled matter. However, mucus can also adsorb small drug molecules administered as aerosols, including antibiotics, thereby reducing their bioavailability. The efficacy of antibiotics is typically assessed by determining the MIC using in vitro assays. This widespread technique, however, does not consider either bacterial biofilm formation or the influence of mucus, both of which may act as diffusion barriers, potentially limiting antibiotic efficacy. Methods: We grew P. aeruginosa biofilms in the presence or absence of human tracheal mucus and tested their susceptibility to tobramycin and colistin. Results: A significant reduction of tobramycin efficacy was observed when P. aeruginosa biofilms were grown in the presence of mucus compared with those grown in the absence of mucus. Diffusion of tobramycin through mucus was reduced; however, this reduction was more pronounced in biofilm/mucus mixtures, suggesting that biofilms in the presence of mucus respond differently to antibiotic treatment. In contrast, the influence of mucus on colistin efficacy was almost negligible and no differences in mucus permeability were observed. Conclusions: These findings underline the important role of mucus in the efficacy of anti-infective drugs.
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J Antimicrob Chemother. 2018;73(10):2762-2769. doi:10.1093/jac/dky241.
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en
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1460-2091
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Attribution-NonCommercial-ShareAlike 4.0 International