Hyperbaric oxygen sensitizes anoxic Pseudomonas aeruginosa biofilm to ciprofloxacin

Mette Kolpen, Christian Johann Lerche, Kasper Nørskov Kragh, Thomas Sams, Klaus Koren, Anna S. Jensen, Laura Line, Thomas Bjarnsholt, Oana Ciofu, Claus Ernst Moser, Michael Kühl, Niels Høiby, Peter Østrup Jensen

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Abstract

Chronic Pseudomonas aeruginosa lung infection is characterized by the presence of endobronchial antibiotic-tolerant biofilm, which is subject to strong oxygen (O2) depletion due to the activity of surrounding polymorphonuclear leukocytes. The exact mechanisms affecting the antibiotic susceptibility of biofilms remain unclear, but accumulating evidence suggests that the efficacy of several bactericidal antibiotics is enhanced by stimulation of aerobic respiration of pathogens, while lack of O2 increases their tolerance. In fact, the bactericidal effect of several antibiotics depends on active aerobic metabolism activity and the endogenous formation of reactive O2 radicals (ROS). In this study, we aimed to apply hyperbaric oxygen treatment (HBOT) to sensitize anoxic P. aeruginosa agarose biofilms established to mimic situations with intense O2 consumption by the host response in the cystic fibrosis (CF) lung. Application of HBOT resulted in enhanced bactericidal activity of ciprofloxacin at clinically relevant durations and was accompanied by indications of restored aerobic respiration, involvement of endogenous lethal oxidative stress, and increased bacterial growth. The findings highlight that oxygenation by HBOT improves the bactericidal activity of ciprofloxacin on P.

OriginalsprogEngelsk
Artikelnummere01024-17
TidsskriftAntimicrobial Agents and Chemotherapy
Vol/bind61
Udgave nummer11
Antal sider9
ISSN0066-4804
DOI
StatusUdgivet - nov. 2017

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