TY - JOUR
T1 - Human airway mucus alters susceptibility of Pseudomonas aeruginosa biofilms to tobramycin, but not colistin
AU - Müller, Laura
AU - Murgia, Xabier
AU - Siebenbürger, Lorenz
AU - Börger, Carsten
AU - Schwarzkopf, Konrad
AU - Sewald, Katherina
AU - Häussler, Susanne
AU - Braun, Armin
AU - Lehr, Claus-Michael
AU - Hittinger, Marius
AU - Wronski, Sabine
PY - 2018/10/1
Y1 - 2018/10/1
N2 - 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.
AB - 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.
KW - Anti-Bacterial Agents/pharmacology
KW - Biofilms/drug effects
KW - Colistin/pharmacology
KW - Humans
KW - Microbial Sensitivity Tests
KW - Mucus/metabolism
KW - Pseudomonas aeruginosa/drug effects
KW - Tobramycin/pharmacology
KW - Trachea/metabolism
U2 - 10.1093/jac/dky241
DO - 10.1093/jac/dky241
M3 - Journal article
C2 - 29982453
SN - 0305-7453
VL - 73
SP - 2762
EP - 2769
JO - The Journal of antimicrobial chemotherapy
JF - The Journal of antimicrobial chemotherapy
IS - 10
ER -