Mechanism of high susceptibility of iron-overloaded mouse to Vibrio vulnificus infection

Vibrio vulnificus produces fulminant septicemia in humans with underlying c onditions, particularly those with diseases that elevate the iron level. Th e effect of a high iron level on the virulence of V. vulnificus was therefo re investigated in mice treated with iron dextran, The mice loaded with iro n became highly susceptible to V. vulnificus infection, the LD50 (50% letha l dose) decreased five logs when infected per peritoneum, However, when inf ected via the oral route, the LD50 was affected little unless the mouse was treated with an additional drug such as cyclophosphamide or D-galactosamin e. Mice with or without iron-overloading died when the bacterial concentrat ion in the blood reached 10(5) cfu/ml or above. Iron increased the growth r ate of the bacteria, both inside and outside of the animal, quickly reachin g a lethal concentration in the iron-overloaded mouse. V. vulnificus, grown with or without the addition of iron, showed strong cytotoxicity on the is olated cells or within the animal at high bacterial concentration, Iron ove rload stimulated the production of tumor necrosis factor alpha (TNF-alpha), a major factor of septic shock, in mice upon infection with the bacteria, probably caused by the endotoxin; however, the neutrophils, whose migration is effected by TNF-alpha, appeared to be less active. Taken together, the major virulence factor of V. vulnificus appeared to be the accelerated grow th of bacteria to quickly reach the lethal level and the lower activity of immune cells including neutrophil as a result of iron-overloading, These tw o effects manifest other virulence factors, the host's as well as bacterial . Such factors, other than TNF-alpha stimulated by the endotoxin, enhanced cytotoxicity, which kills the host cells including the host's immune cells.