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

Authors
 Daniel J. Hassett  ;  John Cuppoletti  ;  Bruce Trapnell  ;  Sergei V. Lymar  ;  John J. Rowe  ;  Sang Sun Yoon  ;  George M. Hilliard  ;  Kislay Parvatiyar  ;  Moneesha C. Kamani  ;  Daniel J. Wozniak  ;  Sung-Hei Hwang  ;  Timothy R. McDermott  ;  Urs A. Ochsner 
Citation
 ADVANCED DRUG DELIVERY REVIEWS, Vol.54(11) : 1425-1443, 2002 
Journal Title
ADVANCED DRUG DELIVERY REVIEWS
ISSN
 0169-409X 
Issue Date
2002
MeSH
Alginates/metabolism ; Anaerobiosis ; Anti-Bacterial Agents/therapeutic use* ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Biofilms/growth & development* ; Chronic Disease ; Cystic Fibrosis/microbiology* ; Glucuronic Acid ; Hexuronic Acids ; Humans ; Ligases ; Mucus/microbiology ; Nitric Oxide/metabolism ; Porins/metabolism ; Pseudomonas Infections/drug therapy* ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/metabolism* ; Pseudomonas aeruginosa/physiology ; Respiratory System/microbiology* ; Transcription Factors/metabolism
Keywords
Pseudomonas aeruginosa ; Anaerobic growth ; Cystic fibrosis
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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0169409X02001527
DOI
10.1016/S0169-409X(02)00152-7
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144739
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