The Implication of Pseudomonas aeruginosa Biofilms in Infections

Morten      T. Rybtke; Peter      O. Jensen; Niels      Hoiby; Michael      Givskov; Tim      Tolker-Nielsen; Thomas      Bjarnsholt

Abstract

Biofilm formation by bacteria is recognized as a major problem in chronic infections due to their recalcitrance against the immune defense and available antibiotic treatment schemes. The opportunistic pathogen Pseudomonas aeruginosa has drawn special attention in this regard due to its severity of infection in the lungs of cystic fibrosis patients and in chronic wounds. In this review we address the molecular basis of biofilm development by P. aeruginosa as well as the mechanisms employed by this bacterium in the increased tolerance displayed against antimicrobials. The complex build-up of the extracellular matrix encasing the biofilm-associated bacteria as well as the elaborate signaling mechanisms employed by the bacterium enables it to withstand the continuous stresses imposed by the immune defense and administered antibiotics resulting in a state of chronic inflammation that damages the host. The immune response leading to this chronic inflammation is described. Finally, novel treatment strategies against P. aeruginosa are described including quorum-sensing inhibition and induced biofilm-dispersion. The tolerance towards currently available antimicrobials calls for development of alternative treatment strategies where the underlying targets are less prone for resistance development as bacteria, in retrospect, have a unique ability to evade the actions of classic antibiotics.

Keywords: Pseudomonas aeruginosa, biofilm formation, chronic infections, inflammatory response, anti-biofilm targets, quorum-sensing inhibition, biofilm-dispersion, cystic fibrosis patients, DAPI stained