Pulmonary dehydration and infection in cystic fibrosis: evidence that ethanol activates alginate gene expression and induction of mucoidy in Pseudomonas aeruginosa.
Mortality among cystic fibrosis (CF) patients is most commonly attributed to pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa. The initial infecting P. aeruginosa are typically non-mucoid; however, upon continued exposure to the CF lung environment, they become highly mucoid. The CF lung is an osmotically high environment because of the presence of substantial concentrations of electrolytes and dehydrated mucus. In this report we demonstrate that ethanol (a commonly used dehydrating agent) activates transcription from a critical alginate promoter, algD, and show that prolonged exposure to ethanol allows switching to the mucoid form. This activation appears to be dependent on DNA gyrase. Analysis of alginate gene activation, and the subsequent reversal of the activation process by bacterial DNA gyrase inhibitors, should aid the development of treatment strategies for CF patients infected with this organism.
DeVault
J D
JD
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago 60612.
Kimbara
K
K
Chakrabarty
A M
AM
D000464:Alginates / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000502:physiology; D004269:DNA, Bacterial / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000502:physiology; D009088:Mucoproteins / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
D000464:Alginates; D004269:DNA, Bacterial; D009088:Mucoproteins; D000431:Ethanol; D004250:DNA Topoisomerases, Type II