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Improved Enzyme Protection Assay to Study Staphylococcus aureus Internalization and Intracellular Efficacy of Antimicrobial Compounds
Published on: September 8, 2021
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
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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