ANTIBACTERIAL ACTIVITY 553 



piration. Quinones often exhibit a diphasic action on respiration (see page 

 488), but information on bacteria is lacking. 



Susceptibilities of Gram-Positive and Gram-Negative Bacteria 



Geiger (1946) stated that the quinones are 50-200 times more inhibitory 

 to gram-positive than to gram-negative bacteria, and similar differences 

 have been observed by many workers. It is evident in the curves of Fig. 5-8. 

 Actually the difference between the gram-positives and gram-negatives 

 may not be as great as Geiger estimated, although in his experiments an 

 average activity ratio near 60 was obtained (comparing StapJnjlococcus 

 aureus and Bacillus subtilis with Escherichia coli and Aerobacter aerogenes), 

 since an average activity ratio of only 2.3 can be calculated in the 

 work of Alcalay (1947 a) (comparing S. aureus, Mycobacterium phlei, 

 and Mycobacterium tuberculosis with E. coli and Shigella flexneri). The 

 data of Kavanagh (1947) provide an intermediate activity ratio of near 

 23 (comparing S. aureus, B. subtilis, Bacillus mycoides, and M. phlei with 

 E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa). The variance 

 in the ratios may be due in part to the media used for the growth of the 

 various organisms, and possibly to some extent to the different types of 

 quinone used (e. g., Geiger tested mainly benzoquinones and Alcalay 

 mainly naphthoquinones). It is not immediately clear why Alcalay found 

 so low a sensitivity for S. aureus. For example, six other workers have re- 

 ported a mean value of 0.029 mM (0.01-0.058 mM) for menadione, whereas 

 Alcalay reports 0.71 mM. Yet his values for E. coli are fairly comparable 

 to the results of others. In any event, gram-positives are generally more 

 sensitive than gram-negatives and it is interesting to speculate whether 

 this implies that the quinones interfere with amino acid accumulation or 

 utilization. One also wonders if this indicates an action by a mechanism 

 similar to that for penicillin; it would be worthwhile to determine if re- 

 sistance to the quinones could be induced, and if such resistant organisms 

 would also be resistant to penicillin. 



Relation of Growth Inhibition to Structure 



There is usually no marked difference in the potencies of the quinone and 

 hydroquinone forms (see accompanying tabulation), and this is probably 

 due to the long periods of incubation allowing interconversion; indeed, it 

 is rather surprising that differences are observed at all under aerobic con- 

 ditions. It is difficult to formulate consistent rules correlating potency with 

 addition of groups to the basic quinone nuclei, since not only do different 

 bacteria behave differently but there is often quite marked variability be- 

 tween the results of different workers. This may be illustrated in the com- 



