April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Efficacy of Wall Teichoic Acid Biosynthesis Inhibitor in Ocular Infection Caused by Staphylococcus Aureus
Author Affiliations & Notes
  • T. Suzuki
    Schepens Eye Research Institute, Boston, Massachusetts
  • J. G. Swoboda
    Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts
  • J. Campbell
    Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts
  • S. Walker
    Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts
  • M. S. Gilmore
    Ophthalmology,
    Schepens Eye Research Institute, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  T. Suzuki, None; J.G. Swoboda, None; J. Campbell, None; S. Walker, None; M.S. Gilmore, None.
  • Footnotes
    Support  NIH grant EY017381, EY008289, GM078477, F3178727, Japanese Eye Bank Society, Uehara Memorial Foundation
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 5714. doi:
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      T. Suzuki, J. G. Swoboda, J. Campbell, S. Walker, M. S. Gilmore; Efficacy of Wall Teichoic Acid Biosynthesis Inhibitor in Ocular Infection Caused by Staphylococcus Aureus. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5714.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Antibiotic resistant microbes, including methicillin resistant Staphylococcus aureus (MRSA), have become leading agents of keratitis or endophthalmitis. Thus new strategies for treatment and prevention are needed. Wall teichoic acids (WTAs) are major polyanionic polymers in the cell wall of Staphylococcus aureus. We demonstrated WTAs are important for the full manifestation of virulence by S. aureus in ocular infection in ARVO 2009. A new bacteriostatic compound (1835F03) that inhibits WTA biosynthesis and growth was recently identified. This study was designed to determine whether WTA biosynthesis represents a useful target for a new prophylactic or therapeutic agent.

Methods: : Minimum inhibitory concentrations (MIC) of 1835F03 were determined according to CLSI protocols for S. aureus keratitis isolates. This compound was assessed for toxicity against human cultured corneal epithelial cells (HCEC), and investigated to determine its activity for inhibiting bacterial invasion. To determine the efficacy of 1835F03 in vitro, S. aureus strains was cultured in bovine vitreous humor with 1835F03. Additionally, the virulence of 1835F03 resistant mutants (5,000 CFU) was tested in C57B6 mouse endophthalmitis. Changes in electroretinography (ERG) and histopathology were determined.

Results: : MIC range for 1835F03 were between 2 and 8 µg/mL against keratitis isolates including MRSA. At concentrations above the MIC, 1835F03 did not induce HCEC damage, and significantly reduced bacterial internalization by HCEC. Furthermore 1835F03 was found to be bactericidal in vitreous. Eyes inoculated with 1835F03 resistant mutants retained significantly greater B-wave amplitude per ERG than eyes infected with the wild type parental. Histological examination showed that the retina was not destroyed in the eyes infected with 1835F03 resistant mutants, indicating that they are highly attenuated.

Conclusions: : The WTA biosynthesis pathway of S. aureus is a viable target for treatment and prevention of keratitis and endophthalmitis caused by S. aureus.

Keywords: antibiotics/antifungals/antiparasitics • bacterial disease • endophthalmitis 
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