PNEUMOLYSIN-NEGATIVE MUTANT OF STREPTOCOCCUS-PNEUMONIAE CAUSES CHRONIC BACTEREMIA RATHER THAN ACUTE SEPSIS IN MICE

Pneumolysin is a cytoplasmic virulence factor of Streptococcus pneumon iae that can interfere with phagocyte function in vitro. We have exami ned the effects of pneumolysin in vitro and in vivo and have found tha t it protects intravenously injected pneumococci against infection-ind uced host resistance. We employed a virulent capsular type 2 pneumococ cal strain, D39, and its isogenic pneumolysin-negative mutant, PLN. St rain D39 exhibited exponential net growth in mice (doubling time, 1.4 h); 24 to 28 h after infection with 10(4) CFU, the numbers of pneumoco cci reached 10(9) to 10(10) CFU/ml and the mice died. Strain PLN yield ed identical net growth in mice until reaching 10(6) to 10(7) CFU/ml a t 12 to 18 h postinfection. At this time, the increase in the level of PLN CFU per milliliter ceased and remained constant for several days. PLN exhibited wild-type growth kinetics in mice when coinfected simul taneously with strain D39. This observation suggests that pneumolysin exerts its effects at a distance. By 12 to 18 h postinfection with PLN , mice exhibited the following evidence of an induced inflammatory res ponse: (i) elevated plasma interleukin-6, (ii) a halt in the net growt h of PLN, and (iii) control of the net growth of pneumolysin-producing D39 pneumococci upon subsequent challenge. Our data suggest that pneu molysin plays a critical role in sepsis during the first few hours aft er infection by enabling pneumococci to cause acute sepsis rather than a chronic bacteremia. However, once chronic bacteremia was establishe d, it appeared that pneumolysin was no longer able to act as a virulen ce factor.