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Suzuki, Takashi

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Suzuki

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Takashi

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Suzuki, Takashi

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2010 - 20112

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Author's Publications: search.filters.isAuthorOfPublication.b83bd22c-622e-4071-be8d-2826b8405202

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    In Vitro Antimicrobial Activity of Wall Teichoic Acid Biosynthesis Inhibitors against Staphylococcus aureus Isolates
    (American Society for Microbiology, 2010) Suzuki, Takashi; Swoboda, J. G.; Campbell, J.; Walker, Suzanne Ellem; Gilmore, Michael
    Staphylococcus aureus is the leading cause of invasive and superficial human infections, is increasingly antibiotic resistant, and is therefore the target for the development of new antimicrobials. Compounds (1835F03 and targocil) were recently shown to function as bacteriostatic inhibitors of wall teichoic acid (WTA) biosynthesis in S. aureus. To assess the value of targeting WTA biosynthesis in human infection, it was therefore of interest to verify the involvement of WTA in bacterial binding to human corneal epithelial cells (HCECs) and to assess the activities of inhibitors of WTA biosynthesis against clinical isolates of methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) from cases of human keratitis. The 1835F03 MIC90s were 8 μg/ml for MSSA keratitis isolates and >32 μg/ml for MRSA keratitis isolates. The MIC90 for the analog of 1835F03, targocil, was 2 μg/ml for both MRSA and MSSA. Targocil exhibited little toxicity at concentrations near the MIC, with increased toxicity occurring at higher concentrations and with longer exposure times. Targocil activity was moderately sensitive to the presence of serum, but it inhibited extracellular and intracellular bacteria in the presence of HCECs better than vancomycin. Targocil-resistant strains exhibited a significantly reduced ability to adhere to HCECs.
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    Role of Wall Teichoic Acids in Staphylococcus aureus Endophthalmitis
    (Association for Research in Vision and Ophthalmology (ARVO), 2011) Suzuki, Takashi; Campbell, Jennifer; Swoboda, Jonathan G.; Kahne, Suzanne; Gilmore, Michael
    Purpose: Wall teichoic acids (WTAs) are major polyanionic polymer components of the cell wall of Staphylococcus aureus. However, little is known about their role at the host–pathogen interface, especially in endophthalmitis. This study was designed to investigate the extent to which WTAs contribute to the pathogenicity of S. aureus in models of endophthalmitis and to determine whether there would be value in targeting their biosynthesis as a new therapeutic approach. Methods: S. aureus RN6390 and its isogenic WTA-null mutant (RN6390ΔtarO) were used to evaluate the role of WTAs in endophthalmitis. RN6390 and RN6390ΔtarO were cultured in bovine vitreous humor (VH) in vitro or inoculated into the vitreous chamber of C57B6 mice. Changes in the number of bacteria, organ function as determined by electroretinography (ERG), and histopathologic changes were assessed throughout the course of infection. In addition, the efficacy of WTA biosynthesis inhibitors in VH in vitro was examined. Results: It was observed that a component of VH synergized with WTA biosynthesis inhibitors in vitro and killed the S. aureus. This effect was also seen when mutants incapable of expressing WTA were exposed to VH. The killing activity of VH was lost on treatment with a protease inhibitor. RN6390ΔtarO could not survive in mouse eyes and did not affect organ function, nor was it able to establish endophthalmitis. Conclusions: WTAs are essential cellular constituents for the manifestation of virulence by S. aureus in endophthalmitis, and appears to be a viable target for treating the endophthalmitis caused by S. aureus strains.