The cleavage of immunoglobulin G in vitro and in vivo by a proteinase secreted by the urinary tract pathogen Proteus mirabilis.
Eighteen different strains of Proteus mirabilis were all shown to produce an EDTA-sensitive proteinase of c. 50 kDa that cleaved the heavy chain, but not the light chain, of IgG. Digestion of pure IgG with small amounts of pure P. mirabilis proteinase generated Fabc'2 and Fab'2 fragments; greater amounts generated Fab and Fc fragments that were comparable in size to those generated by pepsin and papain, respectively. Incubation of neutrophils with IgG digested with P. mirabilis proteinase or papain resulted in a marked decrease in the respiratory burst activity of the neutrophils that coincided with cleavage of the IgG into Fab and Fc fragments. Analysis of urine from patients with P. mirabilis urinary tract infection revealed in many the presence of Fab and Fc fragments of IgG indistinguishable in size from those generated by P. mirabilis proteinase. These results indicate that, in P. mirabilis urinary tract infections, the proteinase is secreted and cleaves IgG to fragments that have defective immune effector functions, thereby limiting the effectiveness of the immune response.
Loomes
L M
LM
Department of Pathology, Dundee University Medical School, Ninewells Hospital.
Kerr
M A
MA
Senior
B W
BW
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001437:Bacteriuria / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism; D007128:Immunoglobulin Fragments / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D010206:Papain / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D011512:Proteus Infections / Q000276:immunology / Q000382:microbiology*; D011513:Proteus mirabilis / Q000201:enzymology* / Q000472:pathogenicity; D016897:Respiratory Burst; D014552:Urinary Tract Infections / Q000276:immunology / Q000382:microbiology*
D007070:Immunoglobulin A; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D010450:Endopeptidases; D010206:Papain; D010434:Pepsin A