Activation of interstitial collagenase, MMP-1, by Staphylococcus aureus cells having surface-bound plasmin: a novel role of plasminogen receptors of bacteria.
Plasmin, the enzymatically active form of plasminogen, can activate several matrix metalloproteinases (MMPs). In this study, we investigated the activation of MMP-1, one of the major interstitial collagenases, by plasmin which was generated on the surface of Staphylococcus aureus cells. Plasmin bound to plasminogen receptors on S. aureus degraded the major (125)I-labeled 55-kDa proMMP-1 into the 42-kDa form corresponding to the size of active MMP-1. MMP-1 formed by S. aureus-bound plasmin was also enzymatically active as judged by digestion of the synthetic collagenase substrate, DNP-Pro-Leu-Gly-Leu-Trp-Ala-D-Arg-NH(2). The finding that, in MMP-1 molecules generated either by soluble plasmin or by S. aureus-bound plasmin, the amino-terminal amino acid sequences were identical indicated that the activation mechanisms of the two plasmin forms do not differ from each other. The present observations emphasise and broaden the physiological importance of bacterial plasminogen receptors. In addition to direct proteolytic effects on components of the extracellular matrix, receptor-bound plasmin is also capable of initiating an MMP-1-dependent matrix-degrading enzymatic cascade.
Santala
A
A
Department of Bacteriology and Immunology, the Haartman Institute, P. O. Box 21 (Haartmaninkatu 3), SF-00014 University of Helsinki, Finland.
Saarinen
J
J
Kovanen
P
P
Kuusela
P
P
D001426:Bacterial Proteins / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D005341:Fibrinolysin / Q000494:pharmacology*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D013379:Substrate Specificity; D014774:Virulence
D001426:Bacterial Proteins; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D005341:Fibrinolysin; D020781:Matrix Metalloproteinase 1