Salmonella cytotoxin: a component of the bacterial outer membrane

Salmonella cytotoxin present in cell-free sonic lysates causes rounding and detachment of Chinese hamster ovary (CHO) cells. Although the precise role of this toxin in the pathogenesis of salmonellosis is unclear, cytotoxin production by Salmonella could account for tissue damage or possibly, facilitate invasion. A variety of other bacteria (e.g. Shigella, Escherichia, Legionella) have been shown to form soluble cytotoxins, many of which may be involved in pathogenesis. The data in this report indicate that the Salmonella cytotoxin in cell-free sonic lysates is firmly associated with cell membrane fragments that can be pelleted by ultracentrifugation (270,000 g for 2.4 h). Furthermore, lysozyme treatment of filter-sterilized sonic extracts of Salmonella species followed by isopycnic sucrose gradient ultracentrifugation allowed separation of the outer and inner membrane components. The outer membrane (OM) peak contained the cytotoxic activity when assayed for detachment of CHO cells. The importance of these data resides in the observation that the Salmonella cytotoxin is an outer membrane component. Its mere location places it in a position of direct contact with host cells and suggests a possible role in cell damage and/or invasion. Furthermore, ultracentrifugation provides a method by which much of the Salmonella cytotoxin in sonic extracts can be removed allowing expression of the Salmonella enterotoxin, whose CHO cell elongation effect is usually obscured by the presence of the cytotoxin causing cell rounding and detachment.