In vivo regulation of virulence in Pseudomonas aeruginosa associated with genetic rearrangement.

A chronic pulmonary infection model was used to induce conversion to the mucoid phenotype by Pseudomonas aeruginosa PAO. At 6 months after initial inoculation, organisms isolated from infected lungs demonstrated the mucoid phenotype. Significant decreases (P less than .01) were seen in the levels of exotoxin A, exoenzyme S, phospholipase C, and pyochelin produced by the mucoid P. aeruginosa PAO rat lung isolates that returned to parental levels after reversion to the nonmucoid phenotype. In addition, lipopolysaccharide of the mucoid PAO lung isolates failed to react with serotype B-specific antibody in contrast to the original PAO and the revertant PAO organisms. Digestion of chromosomal DNA and hybridization with P. aeruginosa virulence factor-specific probes demonstrated that conversion to the mucoid phenotype was associated with rearrangement of chromosomal DNA upstream of the exotoxin A gene. Analysis of DNA from revertant organisms revealed hybridization patterns identical to the original PAO organism.