Rickettsial phospholipase a₂ as a pathogenic mechanism in a model of cell injury by typhus and spotted fever group rickettsiae

Phospholipase A₂ activity by typhus group rickettsiae causes hemolysis in vitro. Rickettsial phospholipase A₂ has been proposed to mediate entry into the host cell, escape from the phagosome, and cause injury to host cells by both typhus and spotted fever group rickettsiae. In a rickettsial contact-associated cytotoxicity model, the interaction of Rickettsia prowazekii or R. conorii with Vero cells caused temperature-dependent release of ⁵¹Cr from the cells. Treatment of rickettsiae, but not the cells, with a phospholipase A₂ inhibitor (bromophenacyl bromide) or with antibody to king cobra venom inhibited cell injury. Rickettsial treatment with bromophenacyl bromide inhibited the release of free fatty acids from the host cell. Neither the inhibitor nor antivenom impaired rickettsial active transport of L-lysine. Thus, host cell injury was mediated by a rickettsial phospholipase A₂-dependent mechanism.