558 5. QUINONES 



necessity for a reactive double bond, but in Table 5-9 there are numerous 

 instances which do not conform to a theory based entirely on SH group 

 reaction. For example, 3-methylmenadione is about 12 times more potent 

 than 1,4-naphthoquinone in inhibiting the growth of S. aureus (Page and 

 Robinson, 1943), and the inhibitions exerted by trimethyl-p-benzoquinone, 

 duroquinone, chloranil, and others cannot be attributed to reaction with 

 SH groups. It is quite possible that inactivation of intracellular thiols or 

 reaction with membrane, mitotic, or enzyme SH groups is involved in 

 certain instances, but other factors are obviously important. Accurate 

 correlations here are impeded by the lack of information on the relative 

 rates at which the various bacteriostatic quinones react with thiols or 

 protein SH groups. Another unknown factor is the possible metabolism 

 of certain quinones by bacteria, some perhaps being inactivated rather 

 rapidly so that their true potency is obscured. 



It is interesting that menadione is able to induce the appearance of 

 variants in bacterial cultures. Colwell (1946) noted that stable small colony 

 variants of E. coli are produced regularly by exposure to 0.018-0.145 mM 

 menadione, this being well below the bacteriostatic concentration. These 

 cells ferment sugars slowly, have a depressed acid production, and grow 

 slowly. She felt that this might result from selection of these forms from 

 the original culture, but there was no evidence for this. Clark et al. (1950) 

 reported that menadione can induce penicillin- and streptomycin-resistant 

 strains in S. aureus (see accompanying tabulation). Selection was ruled 



Menadione Number of mutants resistant to: 



out here by the fact that menadione also produces a number of other mu- 

 tations (e. g., small colony variants and some unable to ferment mannitol). 

 The mechanism for this action is not understood but it might imply some 

 action of menadione on chromosomal or enzyme-forming systems, and this 

 could have bearing on growth inhibition. 



There has been very little work on the metabolic effects of the quinones 

 on bacteria and it is thus impossible to determine whether the growth in- 

 hibition has a metabolic basis. Inspection of Table 5-2 shows that only 



