Anaerobic metabolism and quorum sensing by Pseudomonas aeruginosa biofilms in chronically infected cystic fibrosis airways: rethinking antibiotic treatment strategies and drug targets.
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.
Hassett
Daniel J
DJ
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
Cuppoletti
John
J
Trapnell
Bruce
B
Lymar
Sergei V
SV
Rowe
John J
JJ
Yoon
Sang Sun
SS
Hilliard
George M
GM
Parvatiyar
Kislay
K
Kamani
Moneesha C
MC
Wozniak
Daniel J
DJ
Hwang
Sung Hei
SH
McDermott
Timothy R
TR
Ochsner
Urs A
UA
D000464:Alginates / Q000378:metabolism; D000693:Anaerobiosis; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development*; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000382:microbiology*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D008025:Ligases; D009093:Mucus / Q000382:microbiology; D009569:Nitric Oxide / Q000378:metabolism; D018272:Porins / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D012137:Respiratory System / Q000382:microbiology*; D014157:Transcription Factors / Q000378:metabolism
D000464:Alginates; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D006603:Hexuronic Acids; D018272:Porins; C086515:RhlR protein, Pseudomonas aeruginosa; D014157:Transcription Factors; D009569:Nitric Oxide; D020723:Glucuronic Acid; D008025:Ligases; C096955:RHLI protein, Pseudomonas aeruginosa