Pseudomonas Article

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Drug Week

                                                              February

28, 2003

HEADLINE: CYSTIC FIBROSIS: Antibiotic treatment strategies and drug

targets get

another look

   Researchers evaluating antibiotic treatments for

cystic fibrosis think new drugs are needed to address anaerobic

metabolism by Pseudomonas aeruginosa.

    " 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, " said D.J. Hassett

and colleagues, University of Cincinnati, Ohio.

    " 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, " the researchers wrote.

" Furthermore, anaerobic growth favors maintenance of the mucoid,

alginate-overproducing phenotype. "

   As CF patients age, then, " mucoid populations

predominate, indicating that anaerobic bacteria reside in the

inspissated airway mucus, " Hassett and colleagues said.

   They concluded: " 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 and coauthors published their study in

Advanced Drug Delivery Reviews (Anaerobic metabolism and quorum sensing

by Pseudomonas aeruginosa biofilms in chronically infected cystic

fibrosis airways: Rethinking antibiotic treatment strategies and drug

targets. Adv Drug Deliv Rev, 2002;54(11):1425-1443).

Becki

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