Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets.

@article{citeulike:2988159, abstract = {Recent evidence indicates that Pseudomonas aeruginosa residing as biofilms in airway mucus of cystic fibrosis (CF) patients is undergoing anaerobic metabolism, a form of growth requiring gene products that are not utilized during aerobic growth. The outer membrane protein, OprF, and the rhl quorum sensing circuit are two previously unrecognized cellular factors that are required for optimal anaerobic biofilm viability. Without OprF, bacteria grow extremely poorly because they lack nitrite reductase activity while lacking rhlR or rhlI forces bacteria to undergo metabolic suicide by overproduction of nitric oxide. Furthermore, anaerobic growth favors maintenance of the mucoid, alginate-overproducing phenotype. Thus, with increasing age of CF patients, mucoid populations predominate, indicating that anaerobic bacteria reside in the inspissated airway mucus. Because many frontline antibiotics used in the treatment of CF airway disease are either ineffective or show reduced efficacy during anaerobic conditions, we propose development of new drugs to combat anaerobic metabolism by P. aeruginosa for more effective treatment of chronic CF lung infections.}, address = {Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA. daniel.hassett@uc.edu}, author = {Hassett, D. J. and Cuppoletti, J. and Trapnell, B. and Lymar, S. V. and Rowe, J. J. and Yoon, S. S. and Hilliard, G. M. and Parvatiyar, K. and Kamani, M. C. and Wozniak, D. J. and Hwang, S. H. and McDermott, T. R. and Ochsner, U. A. }, citeulike-article-id = {2988159}, issn = {0169-409X}, journal = {Advanced drug delivery reviews}, keywords = {aeruginosa, anaerobic, biofilm, cf}, month = {December}, number = {11}, pages = {1425--1443}, posted-at = {2008-07-11 13:42:45}, priority = {2}, title = {Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12458153}, volume = {54}, year = {2002} }

TY - JOUR ID - citeulike:2988159 L3 - citeulike-article-id:2988159 TI - Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets. JF - Advanced drug delivery reviews VL - 54 IS - 11 SP - 1425 EP - 1443 AD - Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267-0524, USA. daniel.hassett@uc.edu SN - 0169-409X N2 - Recent evidence indicates that Pseudomonas aeruginosa residing as biofilms in airway mucus of cystic fibrosis (CF) patients is undergoing anaerobic metabolism, a form of growth requiring gene products that are not utilized during aerobic growth. The outer membrane protein, OprF, and the rhl quorum sensing circuit are two previously unrecognized cellular factors that are required for optimal anaerobic biofilm viability. Without OprF, bacteria grow extremely poorly because they lack nitrite reductase activity while lacking rhlR or rhlI forces bacteria to undergo metabolic suicide by overproduction of nitric oxide. Furthermore, anaerobic growth favors maintenance of the mucoid, alginate-overproducing phenotype. Thus, with increasing age of CF patients, mucoid populations predominate, indicating that anaerobic bacteria reside in the inspissated airway mucus. Because many frontline antibiotics used in the treatment of CF airway disease are either ineffective or show reduced efficacy during anaerobic conditions, we propose development of new drugs to combat anaerobic metabolism by P. aeruginosa for more effective treatment of chronic CF lung infections. KW - aeruginosa KW - anaerobic KW - biofilm KW - cf AU - Hassett, DJ AU - Cuppoletti, J AU - Trapnell, B AU - Lymar, SV AU - Rowe, JJ AU - Yoon, SS AU - Hilliard, GM AU - Parvatiyar, K AU - Kamani, MC AU - Wozniak, DJ AU - Hwang, SH AU - McDermott, TR AU - Ochsner, UA PY - 2002/12/05/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12458153 ER -