Spreading of Serratia marcescens in experimental keratitis and growth suppression by chicken egg white ovomacroglobulin.

We studied the inhibitory effects of chicken egg white ovomacroglobulin, a broad-spectrum protease inhibitor, and a synthetic protease inhibitory peptide, Bz-GFR-O-mercaptoanilide, on the growth of two strains of Serratia marcescens in a synthetic medium. The growth of the virulent protease-producing strain, S. marcescens kums 3958 (kums 3958), was more rapid than that of the strain producing minimal protease, S. marcescens kums NA (kums NA), and kums 3958 was inhibited in a dose-dependent manner by ovomacroglobulin. The synthetic inhibitor also inhibited the growth of kums 3958 weakly. Dose-dependent enhancement of growth of kums NA was observed in the medium treated with the serratial 56 kilo Dalton protease. By immunohistochemical methods using an antibody to the bacteria, the spreading of kums 3958 was also studied in corneal tissue in experimental keratitis of the guinea pig. In vivo, kums 3958 grew locally, and then spread widely by destroying stromal tissue 7-8 hours after intrastromal injection of the organisms (3 x 10(4) colony-forming units). On the other hand, when kums 3958 mixed with ovomacroglobulin was injected into the cornea, the organisms remained locally in the corneal stroma which showed a lower grade of damage. These results indicate that proteases secreted from S. marcescens destroyed corneal stroma, yielding the organisms enough space for further spreading.