THE POTENT BONE-RESORBING MEDIATOR OF ACTINOBACILLUS-ACTINOMYCETEMCOMITANS IS HOMOLOGOUS TO THE MOLECULAR CHAPERONE GROEL

Actinobacillus actinomycetemcomitans is a Gram-negative bacterium impl icated in the pathology of localized juvenile periodontitis, a conditi on involving rapid destruction of alveolar bone. We have established t hat gentle extraction of this bacterium in saline releases a proteinac eous fraction (which we have termed surface-associated material [SAM]) which has potent osteolytic activity in the murine calvarial bone res orption assay, Fractionation of the SAM has now revealed that activity is associated with a 62-kD protein, This bone-resorbing activity can be blocked by a monoclonal antibody (raised to the whole bacterium) th at is claimed to recognize a protein homologous to the Escherichia coi l molecular chaperone GroEL, Purification of this bone-resorbing prote in to homogeneity has been achieved by a combination of anion exchange , gel filtration, and ATP-affinity chromatography and the NH2-terminal sequence shows > 95% homology to E. coil GroEL, This GroEL homologue is found in the SAM of A, actinomycetemcomitans but is not found in th e osteolytically active SAM from other Gram-negative or Gram-positive bacteria, The GroEL protein from E. coil, but not from Mycobacterium t uberculosis and Mycobacterium leprae, also showed activity in the bone resorption assay, We believe this to be the first observation that a molecular chaperone has the capacity to stimulate the breakdown of con nective tissue.