Bacillus cereus endophthalmitis is the most rapid and severe form of posttraumatic or endogenous endophthalmitis. Despite aggressive antibiotic and surgical intervention, B. Cereus endophthalmitis has a relatively poor prognosis. Clinicians and researchers have attributed the virulence of B. Cereus endophthalmitis to its toxin production; however, surprisingly little specific data relating to ocular virulence and B. Cereus toxin production exists. Relevant studies identifying factors necessary for the ocular virulence of other ocular pathogens compared infections produced by strains isogenically lacking one or more potential virulence determinants. The study of the relationship of B. Cereus toxins to fulminant endophthalmitis will involve such an approach. B. Cereus proteins reported as possible virulence factors in non-ocular systems include hemolysin BL, cereolysin AB, cereolysin O, and collagenase. Clones containing the genetic loci for each potential virulence determinant listed will be generated from a chromosomal library of a B. Cereus clinical endophthalmitis isolate. Isogenic mutants specifically deficient in each determinant will be generated by allele-replacement and transposon-mediated mutagenesis. Each mutant will then be compared with its wild-type strain in an experimental rabbit model of endophthalmitis to identify the specific factors necessary for fulminant endophthalmitis. The results gained from these studies will lead to the identification of specific factors contributing to fulminant B. Cereus endophthalmitis. These studies will facilitate our understanding of this blinding disease and could lead to the development of target-based therapies to be used in combination with antibiotics and surgery.
