Temperature-sensitive mutants of Pseudomonas aeruginosa: isolation and preliminary immunological evaluation

Abstract
The immunogenicity of 2 temperature-sensitive (ts) mutants of P. aeruginosa immunotype 1, isolated and characterized for the development of a safe, live vaccine strain, was evaluated in a mouse protection model. One mutant, A/10/25, had a limited coasting property (i.e., continued replication for 2 divisions) at the nonpermissive temperature (36.degree. C); the other mutant, E/9/9, continued replication for 5 generations after transfer to 36.degree. C. Groups of 3-5 wk old ICR mice were immunized i.p. with various doses of the 2 ts mutants; at various times thereafter, the mice were challenged i.p. with lethal doses of the parental wild type. The more extensive coaster, E/9/9, induced 100% protection at immunizing doses lower than those required for A/10/25 to induce the same protection (1-2 .times. 108 and 6 .times. 108 colony-forming units, respectively). Both ts strains induced significant protection for up to 5 wk after immunization. Evidently, the use of P. aeruginosa ts mutants might provide a novel approach to the prevention of P. aeruginosa colonization of the lungs patients with cystic fibrosis.