Streptococcus pneumoniae is a major cause of bacterial keratitis. Pneumococcal keratitis causes damage that can result in irreversible corneal scarring. The corneal damage seen in pneumococcal keratitis has been attributed mainly to bacterial virulence factors that stimulate an intense host response. Important to pneumococcal keratitis is the production of pneumolysin, a virulence factor capable of cell lysis as well as the activation of complement. In non-ocular infections, the production of pneumolysin is not sufficient to achieve virulence;the organism must also produce a polysaccharide capsule. The role of the capsule in keratitis or other ocular infections has not been established and preliminary data from this laboratory suggests that the capsule may not contribute to ocular virulence. This point is significant because vaccination of patients has been suggested as a means to prevent pneumococcal ocular infections. The research proposed is designed to develop means to limit the damage associated with pneumococcal keratitis. This research consists of using new therapies directed toward the virulence factors responsible for protecting the organism and stimulating the damaging inflammatory response. The immediate aims are to: 1) determine if the capsule is a virulence factor in keratitis, a study that could show that the cornea, unlike vascularized body sites, is susceptible to infection by unencapsulated strains;2) determine if the inhibition of pneumolysin by topical application of a molecule that inhibits its binding to cells will provide protection against inflammation to the infected cornea, a possibility that is supported by preliminary studies;and 3) determine if antibody to pneumolysin can be used actively or passively to limit or prevent the ability of this molecule to induce inflammation with tissue damaging effects. From a public health perspective, bacteria including pneumococcus are becoming increasingly resistant to antibiotics. The development of alternative and novel therapies for bacterial eye infections will help to prevent scarring and loss of the eye.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Anterior Eye Disease Study Section (AED)
Program Officer
Shen, Grace L
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University of Mississippi Medical Center
Schools of Medicine
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Tullos, Nathan A; Thompson, Hilary W; Taylor, Sidney D et al. (2013) Modulation of immune signaling, bacterial clearance, and corneal integrity by toll-like receptors during streptococcus pneumoniae keratitis. Curr Eye Res 38:1036-48
Taylor, Sidney D; Sanders, Melissa E; Tullos, Nathan A et al. (2013) The cholesterol-dependent cytolysin pneumolysin from Streptococcus pneumoniae binds to lipid raft microdomains in human corneal epithelial cells. PLoS One 8:e61300
Norcross, Erin W; Sanders, Melissa E; Moore 3rd, Quincy C et al. (2011) Pathogenesis of A Clinical Ocular Strain of Streptococcus pneumoniae and the Interaction of Pneumolysin with Corneal Cells. J Bacteriol Parasitol 2:108
Norcross, Erin W; Sanders, Melissa E; Moore 3rd, Quincy C et al. (2011) Active Immunization with Pneumolysin versus 23-Valent Polysaccharide Vaccine for Streptococcus pneumoniae Keratitis. Invest Ophthalmol Vis Sci 52:9232-43
Sanders, Melissa E; Norcross, Erin W; Robertson, Zachary M et al. (2011) The Streptococcus pneumoniae capsule is required for full virulence in pneumococcal endophthalmitis. Invest Ophthalmol Vis Sci 52:865-72
Norcross, Erin W; Tullos, Nathan A; Taylor, Sidney D et al. (2010) Assessment of Streptococcus pneumoniae capsule in conjunctivitis and keratitis in vivo neuraminidase activity increases in nonencapsulated pneumococci following conjunctival infection. Curr Eye Res 35:787-98
Sanders, Melissa E; Norcross, Erin W; Moore 3rd, Quincy C et al. (2010) Immunization with pneumolysin protects against both retinal and global damage caused by Streptococcus pneumoniae endophthalmitis. J Ocul Pharmacol Ther 26:571-7
Sanders, Melissa E; Tullos, Nathan A; Taylor, Sidney D et al. (2010) Moxifloxacin and cholesterol combined treatment of pneumococcal keratitis. Curr Eye Res 35:1142-7
Moore 3rd, Quincy C; McCormick, Clare C; Norcross, Erin W et al. (2009) Development of a Streptococcus pneumoniae keratitis model in mice. Ophthalmic Res 42:141-6
Green, Sherrina N; Sanders, Melissa; Moore 3rd, Quincy C et al. (2008) Protection from Streptococcus pneumoniae keratitis by passive immunization with pneumolysin antiserum. Invest Ophthalmol Vis Sci 49:290-4

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