A New Target for Staphylococcus aureus Associated With Keratitis

Staphylococcus aureus is a leading cause of keratitis, with an increased number of isolates exhibiting antibiotic resistance. Therefore, we need to understand the present situation regarding drug-resistant S. aureus in the ocular site. It has been shown that 35% of S. aureus isolates from ocular sites are methicillin-resistant Staphylococcus aureus (MRSA). MRSA isolates from ocular sites have a high rate of multiple mutations and high levels of resistance against fluoroquinolones. Wall teichoic acids (WTAs) are major polyanionic polymers in the cell wall of S. aureus and are likely to be important in the pathogenesis of eye infection. A new compound, targocil, was recently shown to function as a bacteriostatic inhibitor of WTA biosynthesis in S. aureus. The minimum inhibitory concentration (MIC) at which 90% of the keratitis isolates are inhibited (MIC90) by targocil was 2 mu g/mL for both MRSA and methicillin-sensitive Staphylococcus aureus. Targocil exhibited little toxicity at concentrations near the MIC, with increased toxicity at higher concentrations and longer exposure times. Targocil inhibited intracellular bacteria in the presence of human corneal epithelial cells to a greater extent than vancomycin. Targocil-resistant strains exhibited a significantly reduced ability to adhere to human corneal epithelial cells (P < 0.001). The WTA biosynthesis pathway of S. aureus appears to be a viable target for preventing keratitis caused by strains of this bacterium.