Among the Gram-negative bacilli which cause bacteremia in patients with burns or neutropenia, Pseudomonas aeruginosa is the most vicious, with a fatal outcome in more than 60% of patients. There is a unique tissue reaction associated with P. aeruginosa in these cases - a noninflammatory invasion of blood vessel walls by myriads of bacteria, with subsequent vessel destruction, thrombosis and infarction of surrounding tissue. Since this lesion (known as ecthyma gangrenosum) provides a "permanent" intravascular nidus of necrotizing infection which is difficult to eradicate, it could account for the special virulence of P. aeruginosa. The aim of the proposed research is to uncover the mechanism by which P. aeruginosa accumulates in vessel walls and to determine the importance of ecthyma in virulence. Using neutropenic rabbits we have shown that P. aeruginosa strains of widely differing phenotypes all cause vasculitis when injected directly, but that motility and bacterial toxins and enzymes may be critical to invasiveness from mucous membranes. We plan now to examine the interaction of circulatory factors and bacterial metabolism a) by producing vasculitis in vitro in tissue perfused under a variety of conditions and b) by observing the short-term fate of high inocula in mice with varying states of oxygenation.