Monday, March 28, 2011

Understanding Cystic Fibrosis: Biofilm

There was a recent conversation on CysticLife regarding sputum cultures and their effectiveness in determining the right course of antibiotics. This conversation then led into a short discussion about biofilm which got me thinking that many of us probably aren't that familiar with what it is and what it has to do with Cystic Fibrosis. In my quest for all of us to understand this disease a little bit better, I wanted to post the abstract and conclusion from a recent research article that I read regarding biofilm. Enjoy!

You can find the full article on or by clicking here (you must sign up for a free account to view the entire article)


The persistence of chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients is due to biofilm-growing mucoid (alginate-producing) strains. A biofilm is a structured consortium of bacteria, embedded in a self-produced polymer matrix consisting of polysaccharide, protein and DNA. In CF lungs, the polysaccharide alginate is the major part of the P. aeruginosa biofilm matrix. Bacterial biofilms cause chronic infections because they show increased tolerance to antibiotics and resist phagocytosis, as well as other components of the innate and the adaptive immune system. As a consequence, a pronounced antibody response develops, leading to immune complex-mediated chronic inflammation, dominated by polymorphonuclear leukocytes. The chronic inflammation is the major cause of the lung tissue damage in CF. Biofilm growth in CF lungs is associated with an increased frequency of mutations, slow growth and adaptation of the bacteria to the conditions in the lungs, and to antibiotic therapy. Low bacterial metabolic activity and increase of doubling times of the bacterial cells in CF lungs are responsible for some of the tolerance to antibiotics. Conventional resistance mechanisms, such as chromosomal β-lactamase, upregulated efflux pumps, and mutations of antibiotic target molecules in the bacteria, also contribute to the survival of P. aeruginosa biofilms. Biofilms can be prevented by early aggressive antibiotic prophylaxis or therapy, and they can be treated by chronic suppressive therapy.

Conclusion & Future Perspective

Pseudomonas aeruginosa adapts to the respiratory zone and to the innate and adaptive defense mechanisms of the lungs by forming mucoid biofilms, which survive for decades, in spite of the inflammatory response, where the lung tissue is gradually destroyed. P. aeruginosa also adapts to intense antibiotic therapy by forming mucoid biofilms, but also by conventional resistance mechanisms, which act synergistically to allow P. aeruginosa to survive. P. aeruginosa adapts to the anaerobic conditions in sputum in the conductive zone of the lungs by splitting-off nonmucoid variants, which do not form biofilm in CF patients and, probably, do not play any major clinical role. Biofilm formation is, therefore, the major survival mechanism of P. aeruginosa in the lungs of CF patients, and it is the clinically most important mechanism.

A promising new strategy may be to target biofilm formation by the use of enzymes and other chemicals, such as polyvalent anions, which can dissolve the biofilm matrix (e.g., DNase and alginate lyase). Also, QS inhibitors increase biofilm susceptibility to antibiotics. Induction of neutralizing antibodies against chromosomal β-lactamase of P. aeruginosa improves the clinical outcome of antibiotic therapy with β-lactam antibiotics.This strategy, therefore, may be utilized clinically in the future to neutralize one of the important conventional resistance mechanisms. Possible prophylactic measures could also be use of anti-inflammatory drugs, or antioxidant therapy to prevent ROS-induced mutations in the mucA gene, or use of macrolides, such as azithromycin, in doses that inhibit QS and alginate synthesis, as suggested by in vitroresults and animal experiments.