222 



1. MALONATE 



observed with Diplococcus, Staphylococcus, and Proteus. That is, an infec- 

 tion which does not kill plus a dose of malonate which is non-toxic may 

 cause the death of all the animals within several hours (Berry et al., 1954 a). 

 This is a true case of synergism. It has been found that Salmonella bactere- 

 mia in mice is much greater in malonate-treated animals than in the con- 

 trols (Berry and Mitchell, 1953 b, 1954). The bacteremia in the controls 

 reaches a low peak value soon after inoculation and then falls off, whereas 

 in the presence of malonate it continues to progress. At 9 hr, the blood of 



No. 10 

 Dead 



24 30 36 42 48 



Time after injection ( Hours) 



Fig. 1-20 Effect of malonate given in 8 hourly injections of 20 mg 

 sodium malonate on the mortality of mice intraperitoneally in- 

 jected with suspensions of Salmonella typhimurium . (From Berry 

 and Mitchell, 1953 a.) 



the controls contains 10,000 to 20,000 bacteria/ml whereas the blood of 

 malonate-treated animals has a count of around 3,000,000 bactcria/ml. 

 Thus the bacteremia is over 100-fold as severe in the treated animals as in 

 the controls. This bacteremia is a reflection of the situation throughout 

 the body. The total number of bacteria in the body 6.5 hr after the injec- 

 tions is 1.65 X 10^ in the controls and 32.1 X 10^ in the malonate-treated 

 mice (Berry, 1955). The ratio of counts in the treated and control series is 

 20 for the whole body and 19 for the blood at this time. Now, the interesting 

 thing is that, at the time of death, the number of bacteria in the body is 

 the same in both the controls and malonate-treated mice. This clearly shows 

 that malonate does not alter the susceptibility of the mice to the bacteria, 

 but reduces the time required for the bacteria to multiply to that number 

 necessary to kill. 



