ANTIBACTERIAL ACTIVITY 559 



two bacterial enzymes have been shown to be potently inhibited — there 

 is almost complete inhibition of the NAD(P)H:nitrate oxidoreductase from 

 Achromobacter fischeri by 0.03 TaM menadione and of the pyruvate oxidase 

 from Neisseria gonococcus by 0.03 mM p-benzoquinone — but actually 

 very few enzymes have been examined. Hoffmann-Ostenhof and col- 

 laborators have found little or no correlation between growth inhibition 

 and the effects on various enzymes, but unfortunately most of these en- 

 zymes are unrelated to metabolic systems of importance to bacteria. Me- 

 nadione is able to uncouple oxidative phosphorylation in particulate frac- 

 tions from bacteria (see page 479) and protein synthesis is depressed, but 

 it is not known if these actions are related in any way to bacteriostasis. 

 In no case has a series of quinones been tested on both growth and some 

 enzyme or metabolic activity in order to establish a possible correlation. 

 Growth appears to be suppressed more readily than is respiration, from 

 the meager results available. Thus Vogler et al. (1942) found that p-henzo- 

 hydroquinone prevents growth of Thiobacillus thiooxidans at 0.01-0.1 mM, 

 these concentrations presumably not altering respiration. Finally, there is 

 no evidence to suggest a common mechanism of growth inhibition, and it 

 is perhaps preferable at the present time to assume that various types of 

 quinone act primarily in different ways. 



Effects on Bacterial Infections 



Quinones were tested for their germicidal and antiseptic activity many 

 years ago but they have not proved to be clinically useful, due mainly to 

 the fact that bactericidal concentrations are much higher than bacteriostatic 

 concentrations. For example, p-benzohydroquinone inhibits the growth of 

 *S. aureus at 0.032 mM but 2 mM is required for a cidal action (Yamada and 

 Yanagita, 1957). Although p-benzoquinone was the most effective bac- 

 tericidal substance examined by Thalhimer and Palmer (1911), having 

 a phenol coefficient of 160 against Salmonella typhosa, it still required 

 0.58 mM to be disinfectant after 15-min exposure. The results of the use 

 of the quinones in the treatment of systemic infections have been gener- 

 ally negative. Thus 3,5-dimethoxytoluquinone, despite its effectiveness 

 against certain bacteria in vitro, does not protect mice inoculated with 

 streptococci (Barber, 1944) or staphylococci (Glock et al., 1945). Even 

 the antibiotic quinones, such as spinulosin or fumigatin, have not been 

 found able to protect mice againt pneumococci (Huisman, 1950) and have 

 not proved clinically useful. Two positive results have been reported but 

 have not been adequately followed up. Alcalay (1947 b) administered 

 2-hydroxy-3-chloro-l,4-naphthoquinone orally to guinea pigs with tuber- 

 cular infections, and found a reduction of the weight loss and a prolonged 

 survival of the animals. Del Vecchio (1948 a) tested many quinones in 

 vitro against Brucella and found 6-hydroxymenadione to be particularly 



