The major extracellular protease of the nosocomial pathogen Stenotrophomonas maltophilia: characterization of the protein and molecular cloning of the gene.
Stenotrophomonas maltophilia is increasingly emerging as a multiresistant pathogen in the hospital environment. In immunosuppressed patients, these bacteria may cause severe infections associated with tissue lesions such as pulmonary hemorrhage. This suggests proteolysis as a possible pathogenic mechanism in these infections. This study describes a protease with broad specificity secreted by S. maltophilia. The gene, termed StmPr1, codes for a 63-kDa precursor that is processed to the mature protein of 47 kDa. The enzyme is an alkaline serine protease that, by sequence homology and enzymic properties, can be further classified as a new member of the family of subtilases. It differs from the classic subtilisins in molecular size, in substrate specificity, and probably in the architecture of the active site. The StmPr1 protease is able to degrade several human proteins from serum and connective tissue. Furthermore, pan-protease inhibitors such as alpha(1)-antitrypsin and alpha(2)-macroglobulin were unable to abolish the activity of the bacterial protease. The data support the interpretation that the extracellular protease of S. maltophilia functions as a pathogenic factor and thus could serve as a target for the development of therapeutic agents.
Windhorst
Sabine
S
Universitätsklinikum Hamburg-Eppendorf, D-20246 Hamburg, Germany.
Frank
Eva
E
Georgieva
Dessislava N
DN
Genov
Nicolay
N
Buck
Fritz
F
Borowski
Peter
P
Weber
Wolfgang
W
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D003428:Cross Infection / Q000382:microbiology*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006868:Hydrolysis; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020615:Stenotrophomonas maltophilia / Q000201:enzymology* / Q000472:pathogenicity
D007328:Insulin; D012697:Serine Endopeptidases