Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 54, Issue 11, Pages 1425-1443Publisher
ELSEVIER
DOI: 10.1016/S0169-409X(02)00152-7
Keywords
Pseudomonas aeruginosa; anaerobic growth; cystic fibrosis
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Funding
- NIAID NIH HHS [AI-40541] Funding Source: Medline
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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. (C) 2002 Elsevier Science B.V. All rights reserved.
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