Accessory gene regulator controls Staphylococcus aureus virulence in endophthalmitis

Area of Science:

• Ophthalmology
• Microbiology
• Infectious Diseases

Background:

• Staphylococcus aureus is a common cause of bacterial endophthalmitis.
• The global regulator locus agr controls the expression of numerous toxins and exoproteins in S. aureus.
• The role of S. aureus toxins in the pathogenesis of endophthalmitis requires further elucidation.

Purpose of the Study:

• To investigate the contribution of S. aureus toxins to the severity of experimental endophthalmitis.
• To compare the pathogenicity of wild-type S. aureus with an agr-deficient strain.

Main Methods:

• Experimental endophthalmitis was induced in rabbit eyes using wild-type S. aureus ISP479 and an isogenic agr-deficient strain (ISP546).
• Infections were assessed using electroretinography (ERG), slit lamp biomicroscopy, and histology.
• Two bacterial concentrations (approx. 10 and 1000 organisms) were used for inoculation.

Main Results:

• The agr-deficient strain showed a slower loss of b-wave response on ERG compared to the wild-type strain.
• Lower inoculum (10 organisms) of the agr-deficient strain resulted in less severe clinical signs at 24 and 48 hours.
• Histology at 36 hours revealed focal retinal destruction with wild-type S. aureus but normal retinas with the agr-deficient strain.
• At 100% b-wave loss, histological retinal changes were indistinguishable between groups.

Conclusions:

• Toxin production by S. aureus significantly contributes to the severity of endophthalmitis.
• S. aureus toxins accelerate the onset and progression of retinal damage.
• Early administration of toxin-targeting therapies may be crucial for preserving retinal function in S. aureus endophthalmitis.