Pseudomonas aeruginosa, an opportunistic pathogen, is the major causative agent of mortality and morbidity in immunocompromised patients. It is also the most important pathogen of patients with cystic fibrosis. During chronic infection, numerous changes have been identified including repression of specific virulence genes and surface changes. In order to identify virulence genes of P. aeruginosa that are important in the infection of CF patients, Dr. Jin developed a selection system similar to the in vivo expression technology first described in Salmonella. Using this system, he has identified three genetic loci that are inducible by tracheal-bronchial mucus from CF patients. These loci include the pyochelin receptor, the migA/B locus which is homologous to genes involved in LPS synthesis and is controlled by a DNA rearrangement switch, and regA a positive regulator of exotoxin A synthesis. In this application, Dr. Jin proposes to focus on the migA/B locus and test the hypothesis that the DNA rearrangement in the migA/B locus is responsible for the LPS and exotoxin A phase variation observed in chronic infection. Experiments are designed to (i) define the function of the migA/B gene, (ii) characterize the molecular mechanism of the migA/B DNA rearrangement, and (iii) assess the importance of the DNA rearrangement in chronic infection of hosts.
