Adaptations of Pseudomonas aeruginosa to the Cystic Fibrosis Lung Environment Can Include Deregulation of zwf Encoding Glucose-6-Phosphate Dehydrogenase

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Dennis E. Ohman (Creator)

Paul V. Phibbs (Creator)

Laura Silo-Suh (Creator)

Sang-Jin Suh (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: Cystic fibrosis (CF) patients are highly susceptible to chronic pulmonary disease caused by mucoid Pseudomonas aeruginosa strains that overproduce the exopolysaccharide alginate. We showed here that a mutation in zwf encoding glucose-6-phosphate dehydrogenase (G6PDH) leads to a 90% reduction in alginate production in the mucoid CF isolate P. aeruginosa FRD1. The main regulator of alginate sigma-22 encoded by algT (algU) plays a small but demonstrable role in the induction of zwf expression in P. aeruginosa. However G6PDH activity and zwf expression were higher in FRD1 strains than in PAO1 strains. In PAO1 zwf expression and G6PDH activity are known to be subject to catabolite repression by succinate. In contrast FRD1 zwf expression and G6PDH activity were shown to be refractory to such catabolite repression. This was apparently not due to a defect in the catabolite repression control (Crc) protein. Such relaxed control of zwf was found to be common among several examined CF isolates but was not seen in other strains of clinical and environmental origin. Two sets of clonal isolates from individual CF patient indicated that the resident P. aeruginosa strain underwent an adaptive change that deregulated zwf expression. We hypothesized that high-level unregulated G6PDH activity provided a survival advantage to P. aeruginosa within the lung environment. Interestingly zwf expression in P. aeruginosa was shown to be required for its resistance to human sputum. This study illustrates that adaptation to the CF pulmonary environment by P. aeruginosa can include altered regulation of basic metabolic activities including carbon catabolism. Originally published Journal of Bacteriology Vol. 187 No. 22 Nov 2005

Additional Information

Publication

Other

Journal of Bacteriology. 187:22(November 2005) p. 7561-7568.

Language: English

Date: 2011

Keywords

Pseudomonas aeruginosa, cystic fibrosis, zwf deregulation

Email this document to