Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis.

PURPOSE To evaluate the contribution of toxins to the severity of Staphylococcus aureus endophthalmitis. METHODS Experimental endophthalmitis was established by injecting rabbit eyes with wild type S. aureus ISP479 and the isogenic attenuated strain, ISP546, defective in expression of the global regulator locus agr. agr regulates expression of at least 19 exoproteins that are potentially important in the pathogenesis of endophthalmitis. Infections were evaluated using electroretinography, slit lamp biomicroscopy, and histology. Two concentrations (approximately 10 and 1000 organisms) of bacteria were injected. RESULTS The 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 hours when 10 organisms were injected. However, when the number of bacteria injected was increased to 1000, earlier onset of clinical signs was observed, with both groups showing maximum cell and flare and a white fundal reflex at 48 hours after infection. Histologic examination of eyes enucleated 36 hours after inoculation revealed that the wild type strain induced focal retinal destruction and mild vitritis, whereas eyes infected with the agr- strain remained completely normal. Histologic examination carried out when loss of B-wave response was 100% revealed that retinal changes for both groups could not be distinguished. CONCLUSIONS These data indicate that toxin production by S. aureus contributes to severity of endophthalmitis by accelerating the rate of onset of retinal damage. Therefore, toxin-targeting therapies instituted early in the course of infection could preserve retinal function.