THE POTENT MITOGEN PASTEURELLA-MULTOCIDA TOXIN IS HIGHLY RESISTANT TOPROTEOLYSIS BUT BECOMES SUSCEPTIBLE AT LYSOSOMAL PH

The susceptibility of the potent mitogen Pasteurella multocida toxin ( PMT) to various proteases was investigated, PMT at a toxin to protease molar ratio of 1:1 was resistant to 8 of the 11 proteases tested afte r one hour, With longer incubation, PMT remained resistant to 7 protea ses, and this correlated with a retention of biological activity, indi cating that PMT might not require proteolytic cleavage at least until it bound to a cell receptor, Previous evidence had suggested that PMT is processed in the cell via an endosome or lysosome, We have shown th at PMT became susceptible to proteolysis when the pH was lowered to 5 or below, This supports the previous suggestion that PMT is processed via a low pH compartment in the cell.