Ocular bacterial infections are universally treated with antibiotics, which can eliminate the organism but cannot reverse the damage caused by bacterial products already present. The three very common causes of bacterial keratitis—Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae—all produce proteins that directly or indirectly cause damage to the cornea that can result in reduced vision despite antibiotic treatment. Most, but not all, of these proteins are secreted toxins and enzymes that mediate host cell death, degradation of stromal collagen, cleavage of host cell surface molecules, or induction of a damaging inflammatory response. Studies of these bacterial pathogens have determined the proteins of interest that could be targets for future therapeutic options for decreasing corneal damage. 1. Introduction The bacterial agents of infectious keratitis that have been studied in considerable detail are three of the most common causes of such infections, namely, Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa [1]. The mechanisms underlying the tissue damage occurring during these infections have been studied in animal models. These infections are initiated by injection of bacteria into the corneal stroma, usually of New Zealand rabbits, or by the application of a topical drop of bacteria to a scarified cornea, usually of a mouse [2]. Important to this research is the relative virulence of three forms of a bacterial strain, namely, the unaltered parent strain, its mutant deficient in a single specific gene coding for a secreted protein, and that same mutant strain following insertion of a functional copy of the mutated gene, a rescued strain. If the parent and rescue strains have statistically equivalent virulence and the mutant has significantly less virulence, then the mutated gene is recognized as a key virulence factor for the cornea [3]. An additional method for establishing a specific gene as a virulence factor is to demonstrate that insertion of this specific gene into a nonpathogenic strain can significantly increase the virulence [3]. These types of genetic analysis of virulence have defined multiple virulence factors for each of the three organisms commonly causing keratitis. The importance of secreted proteins to keratitis can be illustrated by the study of certain nonpathogenic strains of bacteria. One observation that is not generally recognized, but is very important to consider, is that bacteria can be injected into a rabbit cornea and there grow from a small inoculum to millions of
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