ACCESSORY GENE REGULATOR CONTROLS STAPHYLOCOCCUS-AUREUS VIRULENCE IN ENDOPHTHALMITIS

Purpose. To evaluate the contribution of toxins to the severity of Sta phylococcus aureus endophthalmitis. Methods. Experimental endophthalmi tis was established by injecting rabbit eyes with wild type S. aureus ISP479 and the isogenic attenuated strain, ISP546, defective in expres sion of the global regulator locus agr. agr regulates expression of at least 19 exoproteins that are potentially important in the pathogenes is of endophthalmitis. Infections were evaluated using electroretinogr aphy, slit lamp biomicroscopy, and histology. Two concentrations (appr oximately 10 and 1000 organisms) of bacteria were injected. Results. T he agr- strain consistently resulted in slower loss of b-wave response when compared to the wild type strain, irrespective of inoculum size. Clinical signs were less severe among the agr- group at 24 and 48 hou rs when 10 organisms were injected. However, when the number of bacter ia injected was increased to 1000, earlier onset of clinical signs was observed, with both groups showing maximum cell and hare and a white fundal reflex at 48 hours after infection. Histologic examination of e yes enucleated 36 hours after inoculation revealed that the wild type strain induced focal retinal destruction and mild vitritis, whereas ey es infected with the agr- Strain remained completely normal. Histologi c examination carried out when loss of B-wave response was 100% reveal ed that retinal changes for both groups could not be distinguished. Co nclusions. These data indicate that toxin production by S. aureus cont ributes to severity of endophthalmitis by accelerating the rate of ons et of retinal damage. Therefore, toxin-targeting therapies instituted early in the course of infection could preserve retinal function.