Pathogenesis and therapy of ocular microbial infections.

摘要

Staphylococcus aureus and Pseudomonas aeruginosa are two leading causes of severe ocular infections. Damage to ocular tissues is mediated by S. aureus pore-forming toxin, alpha-toxin, or P. aeruginosa secreted proteases. Frequently the antibiotic therapy of S. aureus or P. aeruginosa infection reduces the number of bacteria present, but does not arrest tissue damage mediated by the toxin or protease's action.;The studies undertaken herein analyze: (1) a new model of experimental S. aureus conjunctivitis in a rabbit; (2) a chemical inhibitor to the potent corneal toxin, alpha-toxin; (3) the effectiveness of a new formulation of antibiotic-corticosteroid combination therapy; (4) the effect of the host defense molecule surfactant protein D (SPD) during P. aeruginosa keratitis; (5) a new approach to develop antibody to an important corneal virulence factor, protease IV; and (6) the effect of P. aeruginosa proteases on rabbit tears.;The results show that: (1) degradation a new model of S. aureus experimental conjunctivitis was established, for the analysis of bacterial pathogenesis and the effectiveness of new antibiotics or anti-inflammatory drugs; (2) CD-Cholesterol inhibits the action of alpha-toxin in vitro and topical application of CD-Cholesterol significantly reduces the pathologic effects of S. aureus keratitis without affecting growth of bacteria; (3) in terms of bacterial killing, the combination of tobramycin and dexamethasone in a new vehicle with xanthan gum was superior to these drugs in a standard vehicle; (4) SPD is an important host defense molecule during P. aeruginosa keratitis---mice deficient in SPD experienced significantly more pathology and bacterial growth as compared to mice with functional SPD; (5) antibody to a recombinant form of PIV was obtained after primary immunization, but this antibody was not highly reactive to native PIV; and (6) rabbit tears incubated with P. aeruginosa protease IV (PIV) or alkaline protease underwent massive protein.;These studies evaluated the pathogenesis and therapy of ocular infection and show that SPD and tears are important host defenses against P. aeruginosa infection and that new therapies can limit the damage mediated by ocular infection.