Natural host resistance to Pseudomonas aeruginosa corneal infection is regulated by two complementing dominant genes PsCRl and PsCR2 (RS Berk, MA Leon, LD Hazlett. Infect Immun 26: 122 1-1223, 1979). In this study we have demonstrated a third dominant gene, which determines susceptibility to P. aeruginosa-induced eye damage. This gene was designated as PsCS. The F, progeny from matings between the resistant DBA/2J strain and the susceptible strain C57BL/6J and C3H/HeJ displayed the susceptibility phenotype. Backcross and F2 studies using the C3H/HeJ and DBA/2J strains suggested the presence of two linked PsCS loci. 488

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The ocular damage in mouse pups produced by purified Pseudomonas aeruginosa exotoxin A was examined microscopically following toxin A injection beneath the fused eyelid. In contrast to infection, in which lysis of ocular surface epithelium occurs within minutes, toxin A does not induce any lytic changes until 5 h after injection. Additionally, no phagocytic cellular response to toxin A was observed, whereas in infection, this response is seen within 1 h. We conclude that toxin A is not the bacterial extracellular factor responsible for mediating the rapid early destruction of the ocular epithelium allowing bacterial penetration and dissemination.