Because of the limited access to intraocular spaces by components of the immune system, bacterial endophthalmitis -- resulting from traumatic injury or arising as a post surgical complication -- frequently results in loss of useful vision in the infected eye. The advent of therapeutic measures including vitrectomy and intraocular antibiotic administration has proven valuable in salvaging sight in many eyes that otherwise would be lost to endophthalmitis. However, the prognosis in fulminant cases of endophthalmitis where the offending organism is known to produce cytotoxic factors remains poor. Prior to the development of sophisticated genetic techniques for manipulating bacterial expression of virulence factors, direct assessment of the contribution of cytotoxic bacterial products to disease was impossible. The bacterium Streptococcus (Enterococcus) faecalis provides a unique model for directly determining the role played by a cytotoxin in endophthalmitis for several reasons: 1) the only virulence factor thus far ascribed to the organism is a cytolytic toxin, 2) the cytolytic toxin is encoded by a mobile genetic element amenable to in vitro manipulation, 3) Iosgenic strains of S. faecalis specifically attenuated in expression of the cytolytic toxin have been constructed, and 4) S. faecalis has been observed to cause a significant proportion of more severe endophthalmitis cases and has been identified as the primary etiologic agent in cases involving filtering blebs. The goals of the proposed research are to establish a rabbit model for S. faecalis endophthalmitis and directly test the contribution of the cytolytic toxin in the disease model. Further, other cellular components and products produced by the organism will be tested for their contribution to the histopathology of S. faecalis endophthalmitis. Finally, antibiotic and anti-inflammatory therapies will be compared to assess their relative values in eliminating the infections and minimizing loss of vision.
| Sadaka, Ama; Palmer, Kelli; Suzuki, Takashi et al. (2014) In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection. PLoS One 9:e110872 |
| Van Tyne, Daria; Martin, Melissa J; Gilmore, Michael S (2013) Structure, function, and biology of the Enterococcus faecalis cytolysin. Toxins (Basel) 5:895-911 |
| Suzuki, Takashi; Campbell, Jennifer; Kim, Younghoon et al. (2012) Wall teichoic acid protects Staphylococcus aureus from inhibition by Congo red and other dyes. J Antimicrob Chemother 67:2143-51 |
| Sadaka, Ama; Durand, Marlene L; Gilmore, Michael S (2012) Bacterial endophthalmitis in the age of outpatient intravitreal therapies and cataract surgeries: host-microbe interactions in intraocular infection. Prog Retin Eye Res 31:316-31 |
| Suzuki, Takashi; Campbell, Jennifer; Swoboda, Jonathan G et al. (2011) Role of wall teichoic acids in Staphylococcus aureus endophthalmitis. Invest Ophthalmol Vis Sci 52:3187-92 |
| Suzuki, Takashi; Swoboda, Jonathan G; Campbell, Jennifer et al. (2011) In vitro antimicrobial activity of wall teichoic acid biosynthesis inhibitors against Staphylococcus aureus isolates. Antimicrob Agents Chemother 55:767-74 |
| Klocke, Julia; Barcia, Rita N; Heimer, Susan et al. (2011) Spontaneous bacterial keratitis in CD36 knockout mice. Invest Ophthalmol Vis Sci 52:256-63 |
| Swoboda, Jonathan G; Meredith, Timothy C; Campbell, Jennifer et al. (2009) Discovery of a small molecule that blocks wall teichoic acid biosynthesis in Staphylococcus aureus. ACS Chem Biol 4:875-83 |
| Roux, Agnès; Payne, Shelley M; Gilmore, Michael S (2009) Microbial telesensing: probing the environment for friends, foes, and food. Cell Host Microbe 6:115-24 |
| Whiston, Emily A; Sugi, Norito; Kamradt, Merideth C et al. (2008) alphaB-crystallin protects retinal tissue during Staphylococcus aureus-induced endophthalmitis. Infect Immun 76:1781-90 |
Showing the most recent 10 out of 49 publications
