Staphylococcus aureus is a major cause, if not the leading cause, of bacterial infections of the anterior portion of the human eye. This organism commonly infects the eyelids and conjunctiva and causes sight-threatening infections of the cornea. Such infections of the cornea, even when treated promptly with antibiotics, can still cause extensive tissue damage that often results in reduced vision or blindness. Research in this laboratory has shown that a high percentage of the corneal tissue damage produced by S. aureus is due to the action of bacterial toxins. Killing bacteria with antibiotics does not prevent the action of these damaging toxins once they are released by the bacteria. The long term goal of this research has been to identify the staphylococcal toxins that can damage the eye and to identify new medications that, unlike all existing drugs, can block the action of these toxins. Recent research in this laboratory has dramatically progressed. For the first time, an ocular formulation has been developed that can arrest the action of the most potent ocular toxin produced by S. aureus. This toxin, known as alpha-toxin, can be inhibited by >10,000-fold in vitro and application of this formulation to experimentally infected eyes significantly reduced (by 50% or more) the damaging effects of S. aureus infection. Needed now are tests of the formulation with concurrent antibiotic therapy, a combined therapy expected to achieve a far greater reduction in the ocular damage. Also needed are efforts to: 1) alter the active compound seeking even greater activity, 2) improve delivery of the active component to the eye, and 3) determine the optimum course of therapy. Another major advance toward the long term goals has been the identification and isolation of a previously unknown S. aureus toxin that can disrupt the cornea. Efforts are needed to: 1) characterize the enzymatic action of this toxin, 2) determine the extent of its production by S. aureus isolates, and 3) produce and analyze a mutant lacking the toxin, a mutation that should reduce the corneal virulence. The information from these studies will help determine a formulation that could inhibit the action of this newly discovered corneal toxin.

Public Health Relevance

The research described herein is intended to provide means to protect the anterior eye from the tissue damaging effects of Staphylococcus aureus infections. Corneal infections with S. aureus are among the most common ocular infections that can cause blindness. The findings of this study will hopefully provide a new medication to limit the ocular damage of these potentially blinding infections as well as provide scientific information on a new ocular toxin produced by this highly pathogenic organism.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY010974-15
Application #
8288214
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Mckie, George Ann
Project Start
1996-08-01
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
15
Fiscal Year
2012
Total Cost
$351,648
Indirect Cost
$114,048
Name
University of Mississippi Medical Center
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
928824473
City
Jackson
State
MS
Country
United States
Zip Code
39216
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Dajcs, Joseph J; Thibodeaux, Brett A; Girgis, Dalia O et al. (2002) Immunity to lysostaphin and its therapeutic value for ocular MRSA infections in the rabbit. Invest Ophthalmol Vis Sci 43:3712-6

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