A New Target for Staphylococcus aureus Associated With Keratitis

Abstract

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 μg/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.

Pattern recognition receptors in microbial keratitis

“…A high-affinity human monoclonal antibody to S. aureus α-toxin has been found to be effective at reducing corneal damage 204 and a new antibiotic, targocil, has had some preliminary success at inhibiting the severity of staphylococcal infections. 205 Several potential therapies have been identified in Pseudomonas infection, including lithium chloride 206 and a caspase-1 inhibitor that reduces the amount of IL-1β produced. 207 Factors that improve corneal inflammation include the apoptotic Fas pathway which regulates the production of proinflammatory cytokines 208 and a phospho-inositol-3-kinase (PI3K)/Akt pathway that activates a receptor known as triggering receptor expressed on myeloid cells 2 (TREM-2).…”

Methicillin‐resistant Staphylococcus aureus keratitis in a dog

“…Methicillin‐resistant staphylococci are usually resistant to a large number of commonly used antibiotics (penicillins, cephalosporins, and fluoroquinolones); 16 however, some reports demonstrated that chloramphenicol is effective against MRSA infections 12,17–19 . In the present case also, keratitis associated with MRSA was resolved by topical and systemic treatment with chloramphenicol followed by vancomycin.…”

Linezolid Versus Vancomycin for the Treatment of Methicillin-Resistant Staphylococcus aureus Keratitis in Rabbits

“…Therefore, new antimicrobials with an improved activity against emerging or resistant MRSA strains are of crucial importance. [17][18][19] This study provides the first reported evidence that LZD has the therapeutic potential for the treatment of keratitis caused by MRSA. We found that topical LZD was as effective in reducing CFUs as topical VA. Another interesting finding of the present study is that the epithelial toxicity of LZD was less than that of VA.…”