Mette Kolpen
University of Copenhagen, Denmark
Title: Enhancement of the bactericidal activity of antibiotics in hypoxic biofilms as seen in patients with chronic pulmonary disease.
Biography
Biography: Mette Kolpen
Abstract
Pseudomonas aeruginosa lung infection is among the most severe complication in patients with chronic obstructive pulmonary
disease (COPD) and cystic fibrosis (CF). CF related pulmonary infection is characterized by antibiotic-tolerant biofilms in the
endobronchial mucus with zones of oxygen (O2) depletion mainly due to polymorphonuclear leukocyte (PMN) activity. Despite
anoxic conditions, the flexible metabolism of P. aeruginosa growing in biofilms allows this pathogen to obtain energy for growth by
denitrification as demonstrated by production of nitrous oxide in CF sputum samples. While the exact mechanisms affecting antibiotic
effectiveness on biofilms remain unclear, accumulating evidence suggests that the efficiency of several bactericidal antibiotics such
as ciprofloxacin is enhanced by stimulation of the aerobic respiration of pathogens and that lack of O2 increases their tolerance. Reoxygenation
of O2- depleted biofilms may thus improve susceptibility to ciprofloxacin possibly by restoring aerobic respiration. Such
strategy was then tested using re-oxygenation of O2- depleted P. aeruginosa strain PAO1 agarose embedded biofilms by hyperbaric
O2 treatment (HBOT) enhancing the diffusive supply for aerobic respiration during ciprofloxacin treatment. The demonstration of
enhanced bactericidal activity of ciprofloxacin in P. aeruginosa biofilm during re-oxygenation by hyperbaric O2 treatment (HBOT) is
indeed a proof-of-principle study that may translate into improved treatment of both CF and COPD patients.