THE HEMOLYTIC AND COMPLEMENT-ACTIVATING PROPERTIES OF PNEUMOLYSIN DO NOT CONTRIBUTE INDIVIDUALLY TO VIRULENCE IN A PNEUMOCOCCAL BACTEREMIA MODEL

The virulence of pneumococcal capsular type 2 strain D39 and derivativ es with mutations in the pneumolysin gene were examined in a mouse bac teremia model. In CBA/N-XID mice D39 is known to exhibit exponential g rowth in the blood until the death of the mice at 24 to 36 h. In contr ast, PLN, a pneumolysin-deficient derivative of D39, reaches a plateau in growth that is maintained for several days. The growth patterns of D39 and PLN observed in CBA/N-XID mice were also observed in C3H/HeJ and C3H/HeOuJ mice, but not in 129/SvJ and C57BL/6J mice. These result s demonstrate that the effect of pneumolysin on bacteremia is dependen t on the genetic background of the mice. D39 derivatives with point mu tations which abolish the cytotoxic or complement-activating propertie s of pneumolysin did not have major individual effects on virulence in CBA/N-XID and C3H/HeOuJ mice. A derivative with mutations affecting b oth the cytotoxic and complement-activating properties resulted in a m odest, yet statistically significant, increase in survival time of i.v . challenged CBA/N-XID mice. However, the effect was less marked than that seen with PLN. These findings suggest that the virulence effects of pneumolysin in bacteremia must be due in part to properties other t han hemolysis and complement fixation. (C) 1997 Academic Press Limited .