Pasteurella multocida Toxin and Bordetella bronchiseptica Dermonecrotizing Toxin Elicit Similar Effects on Cultured Cells by Different Mechanisms

Abstract

We compared the effects of Pasteurella multocida toxin (PMT) with Bordetella bronchiseptica dermonecrotizing toxin (DNT) at a cellular level under same conditions. Both PMT and DNT cause actin stress fiber formation in MC3T3-E1 cells which is known to be regulated by the small GTP-binding protein Rho. DNT induced mobility shifts of Rho on SDS-polyacrylamide gel electrophoresis, indicating direct modification as reported elsewhere. In contrast, no alternations in the electrophoretic mobility of Rho were found in lysates from PMT-treated cells. PMT but not DNT increased the intracellular level of inositol phosphates, indicating the elevation of phospholipase C (PLC) activity in the PMT-treated cells. These results indicate that PMT does not have Rho as a target but activates PLC. The formation of actin stress fiber by PMT seems to be stimulated through the indirect activation of Rho, which resides downstream of PLC. PMT and DNT seem to elicit similar toxic effects, at least in part, through the activation of Rho.