Elucidating the molecular mechanisms of bacterial virulence using non-mammalian hosts

Several strains of the human opportunistic pathogen Pseudomonas aeruginosa infect plants, nematodes and insects. Our laboratory has developed a multih ost pathogenesis system based on the P, aeruginosa clinical isolate PA14, i n which non-mammalian hosts are used to screen directly for virulence-atten uated mutants. The majority of PA14 mutants isolated using non-mammalian ho sts also displayed reduced virulence in a burned mouse model. Surprisingly, only a few host-specific ari ru fence facto rs were identified, and many o f the P. aeruginosa mutants were attenuated in virulence in all the hosts. These studies illustrate the extensive conservation in the virulence mechan isms used by P. aeruginosa to infect evolutionarily diverged hosts, and val idate the multihost method of screening for virulence factors relevant to m ammalian pathogenesis, Through the use of genetically tractable hosts, the multihost pathogenesis model also provides tools for elucidating host respo nses and dissecting the fundamental molecular interactions that underlie ba cterial pathogenesis.