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A new target for Staphylococcus aureus associated with keratitis
1Department of Ophthalmology, Ehime University School of Medicine, Toon, Japan. t-suzuki@m.ehime-u.ac.jp
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.
Insights
Targocil effectively inhibits drug-resistant Staphylococcus aureus, a common cause of keratitis. This new compound targets bacterial cell walls, showing promise for treating eye infections caused by resistant strains.
Area of Science:
- Ophthalmology
- Microbiology
- Infectious Diseases
Background:
- Staphylococcus aureus is a primary cause of keratitis.
- A significant percentage (35%) of ocular S. aureus isolates are methicillin-resistant (MRSA).
- MRSA exhibits high resistance to fluoroquinolones, necessitating alternative treatments.
Purpose of the Study:
- To investigate the efficacy of targocil, a novel inhibitor of wall teichoic acid (WTA) biosynthesis, against ocular S. aureus isolates.
- To evaluate targocil's toxicity and its effect on bacterial adherence.
- To assess targocil's potential as a therapeutic agent for keratitis.
Main Methods:
- Determined the minimum inhibitory concentration (MIC90) of targocil for MRSA and methicillin-sensitive S. aureus (MSSA) keratitis isolates.
- Assessed targocil's toxicity in human corneal epithelial cells.
- Compared targocil's efficacy against intracellular bacteria with vancomycin.
- Investigated the adherence of targocil-resistant strains to corneal cells.
Main Results:
- Targocil demonstrated a low MIC90 of 2 μg/mL against both MRSA and MSSA.
- Targocil showed minimal toxicity at therapeutic concentrations, with increased toxicity at higher doses.
- Targocil was more effective than vancomycin in inhibiting intracellular bacteria.
- Targocil-resistant strains displayed significantly reduced adherence to corneal epithelial cells.
Conclusions:
- The WTA biosynthesis pathway is a promising target for combating S. aureus keratitis.
- Targocil presents a potential therapeutic strategy against drug-resistant S. aureus eye infections.
- Reduced bacterial adherence in resistant strains suggests implications for virulence and treatment strategies.
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