BACTERIOSTATIC AND BACTERICIDAL AGENTS 249 



quire the cooperation of succinic dehydrogenase and a cytochrome sys- 

 tem, was strongly inhibited by pyocyanin. This inhibition exhibited cer- 

 tain interesting peculiarities: in low concentrations, pyocyanin strongly 

 inhibited the activity of the complete succinic cytochrome system but 

 had no effect on the oxidation of succinic acid through methylene 

 blucj in the presence of KCN, pyocyanin acted as an autoxidizable hy- 

 drogen acceptor similar to methylene bluej glutaminic acid did not af- 

 fect the inhibitory action of pyocyanin. This inhibitory action was found 

 to be due not to the formation of oxalacetic acid but to a direct effect on 

 succinic dehydrogenase. The influence of pyocyanin on bacterial respira- 

 tion, as well as its ability to function as an accessory respiratory enzyme, 

 has aroused much interest (228, 302). 



A strong lytic action of some of the antibiotic substances, similar in 

 some cases to the action of enzymes, has also been Indicated. This lytic 

 mechanism may be a product of the antagonized cell itself. Autolysis 

 is usually defined as the destruction of some of the essential chemical 

 constituents of the cell by enzymes originating within the cell. 



The lytic effect does not hold true, however, for most of the anti- 

 biotic substances and for most of the bacterial cells. Since the greatest 

 bactericidal effect of penicillin occurs during the maximum rate of bac- 

 terial multiplication and since cells producing autolysin lyse rapidly it 

 must be concluded that lysis of the cells follows the killing effect of 

 penicillin (913). 



Chain and Duthie (121) called attention to the fact that Fleming re- 

 corded the slow bactericidal effect of penicillin on Staphylococcus and 

 its lytic action only under certain conditions. The original statement by 

 Florey, Chain, and associates that penicillin was mainly bacteriostatic 

 was based on the fact that it did not influence the oxygen uptake of rest- 

 ing Staphylococcus y for large numbers of viable colonies were found 

 after incubation with penicillin for 24 hours. Penicillin was later found 

 to be definitely bactericidal, but not under unfavorable conditions such 

 as low temperature or exhausted media. The bactericidal effect can be 

 increased by substances which favor bacterial growth or decreased by 

 substances which interfere with bacterial growth, such as sulfadiazine. 

 During the resting phase of Staphylococcus ^ even large concentrations 

 of penicillin have no effect on the oxygen uptake. However, during the 



