ANTIBACTERIAL ACTIVITY 551 



reliable for several reasons. First, the inhibitory potency will depend on 

 the experimental conditions, particularly the pH, the temperature, and the 

 medium used. For example, the inhibition of Hemophilus ^pertussis growth 

 by p-benzohydroquinone is much reduced in peptone broth relative to a 

 synthetic medium (Grootten and Bezssonoff, 1935), and the activity of 

 3,5-diCH30-TQ against a variety of bacteria is reduced 5-fold in serum 

 broth compared to a glucose broth (Glock et al., 1945). Zetterberg (1949) 

 studied the effects of menadione and phthiocol on mycobacteria in five 

 different media and found great variation in the bacteriostatic concentra- 

 tions. Second, the effectiveness will depend on the density of the bacterial 

 suspension, the lowest concentrations being required with the fewest 

 bacteria (Armstrong et al., 1943). Third, there is variation in sensitivity 

 between strains; this is seen with staphylococci and streptococci (Barber, 

 1944) and particularly well with Brucella melitensis (Del Vecchio et al., 

 1948). Fourth, the bacteriostatic concentration will vary with the time 

 chosen for the test, and different times for incubation with the quinones 

 were used by different investigators; an interval of 24 hr was selected in 

 most instances. Finally, the concentrations are often determined by serial 

 dilution, so that certain values may be somewhat too high. For these 

 reasons comparisons should not be made between the values given by dif- 

 ferent investigators, but the relative activities within a particular study 

 are probably reliable, and hence some information can be obtained on the 

 effects of structural alterations on the antibacterial potency. 



Concentration-Action Relations and Biphasic Effects 



The effects of p-benzoquinone on the growth of four species of bacteria 

 are shown in Fig. 5-8, and the effects of a variety of quinones on the growth 

 of Pseudomonas aeruginosa are shown in Fig. 5-9. One notes that there 

 is commonly a stimulation of growth at lower concentrations. The degree 

 of stimulation may depend on the medium used, since the growth of Pseudo- 

 monas is accelerated maximally around 23% by p-benzoquinone in meat- 

 peptone medium (Fig. 5-8) and only 7% in synthetic medium (Fig. 5-9). 

 The stimulation may be related to reaction with SH groups, inasmuch as 

 such biphasic effects are often seen with SH reagents, or to participation 

 of the quinone in the bacterial metabolism. There seems to be no obvious 

 correlation between the reactivity with SH groups and the ability to stim- 

 ulate growth, not is there a clear relation to the redox potentials of the 

 quinones. The marked stimulating action of 2-chloro-3-hydroxy-l,4-naph- 

 thoquinone is interesting but impossible to explain. It is also evident that 

 the slope of the concentration-action curve for this compound is greater 

 than for most of the other quinones, so that it completely inhibits growth 

 at a lower concentration than any of the other quinones tested. It would 

 be valuable to have data on the effects of these quinones on bacterial res- 



