Pathogenic capacity of proteases from Serratia marcescens and Pseudomonas aeruginosa and their suppression by chicken egg white ovomacroglobulin.
The pathogenicities of three proteases from Serratia marcescens, two proteases from Pseudomonas aeruginosa, and one thermolysin from Bacillus stearothermophilus were examined. All proteases tested caused acute liquefactive necrosis of the cornea and descemetocele formation in guinea pig eyes after intrastromal injection, with the exception of the 60-kilodalton protease from S. marcescens, which produced only an opaque lesion. When injected into guinea pig skin, the protease also enhanced vascular permeability, which was followed by edema formation. The permeability-enhancing activity of the proteases increased in parallel with the concentration of the enzymes. When tested in vitro for its effect on these bacterial proteases, chicken egg white ovomacroglobulin (ovoM) inhibited the enzymatic activity of all the proteases after a short incubation period at an enzyme/inhibitor ratio (molar) of 1:1 to 1:4 or at a lower concentration after a longer incubation period. Such treatment of the proteases with chicken egg white ovoM before injection intrastromally into the eyes or intradermally into the clipped flanks of guinea pigs protected the cornea from destruction or completely prevented the permeability reaction and edema formation. No inhibitory effects of plasma protease inhibitors against these bacterial proteases were noted. Since the proteases are critical in the pathogenic processes caused by the bacteria, these results suggest a beneficial effect of ovoM against bacterial infections.
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D003315:Cornea / Q000187:drug effects / Q000473:pathology; D003316:Corneal Diseases / Q000209:etiology*; D003320:Corneal Ulcer / Q000139:chemically induced; D004487:Edema / Q000209:etiology; D004527:Egg Proteins / Q000494:pharmacology; D005260:Female; D001411:Geobacillus stearothermophilus / Q000201:enzymology / Q000472:pathogenicity; D006168:Guinea Pigs; D006801:Humans; D008259:Macroglobulins / Q000494:pharmacology*; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D011480:Protease Inhibitors; D011550:Pseudomonas aeruginosa / Q000201:enzymology* / Q000472:pathogenicity; D012706:Serratia marcescens / Q000201:enzymology* / Q000472:pathogenicity; D012867:Skin / Q000187:drug effects; D012871:Skin Diseases / Q000209:etiology; D013820:Thermolysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000511:alpha-Macroglobulins
D004527:Egg Proteins; D008259:Macroglobulins; D011480:Protease Inhibitors; D000511:alpha-Macroglobulins; C036828:ovomacroglobulin; D010447:Peptide Hydrolases; D013820:Thermolysin