CONTRIBUTION OF SPECIFIC PSEUDOMONAS-AERUGINOSA VIRULENCE FACTORS TO PATHOGENESIS OF PNEUMONIA IN A NEONATAL MOUSE MODEL OF INFECTION

We sought to identify which Pseudomonas aeruginosa products are involv ed in initiating respiratory tract infection. Defined mutants derived from strain PAO, i.e., PAOR1 (lasR), PAO-pmm (algC) (an LPS mutant), a nd AK1152 (which is Fla(-) and lacks functional pili), were significan tly less virulent than PAO1 in a BALBc/ByJ neonatal mouse model of inf ection as measured by their abilities to cause acute pneumonia, bacter emia, and death. All three mutants were also less adherent to epitheli al cells in an in vitro binding assay. PAOR1 and AK1152 were less able to elicit epithelial production of interleukin-8 than PAO1. LasR was found to be required for the optimal expression of neuraminidase under conditions of increased osmolarity, as might be present in certain pa thological conditions. PAO-exsA::Omega, which lacks exoenzyme S expres sion, was fully virulent, causing at least as much pathology as PAO1. The expression of several P. aeruginosa virulence factors appears to b e required to establish pulmonary infection in the neonatal mouse.