178 ANTIBACTERIAL SUBSTANCES FOR TREATMENT OF INFECTIONS 



In experimental streptococcal and staphylococcal infections, its chief effect was to 

 prolong survival time, but not to prevent death (Chain, Florey, Jennings and Williams 

 1943). 



Penatin. (Notatin). Penatin, as well as penicillin, is produced in cultures of P. nota- 

 tum. An acid medium favours the production of penatin, which can be detected by using 

 BacL coli (which is insusceptible to peniciUin) as the indicator organism in titrations of 

 bacteriostatic power. Penatin is a relatively stable, w^ater -soluble substance, active against 

 Gram-positive and Gram-negative bacteria in dilutions of 1 : 12-5 x 10® to 1 : 250 x 10®. 

 Serum does not interfere with its action. It is active only in the presence of glucose, 

 which it decomposes with the production of HgOj. In animals, it is moderately toxic, 

 with local reactions at the site of injection (Kocholaty 1942, 1943a, b). The same substance 

 was described by Coulthard and his colleagues (1942) under the name of notatin. It is 

 a glucose-aerodehydrogenase, with the properties of a flavoprotein. The presence of 

 oxygen and glucose, and the absence of a catalase, are necessary for its antibacterial 

 activity, which is mainly due to the HgOj produced in these circumstances (Btrkinshaw 

 and Raistrick 1943). A similar substance, PenicUhn B, was extracted from cultures of 

 P. notatum by Roberts and his colleagues (1943). Like notatin, it was a flavoprotein, 

 producing HjOj from glucose, but unhke notatin, the glucose could be replaced by xylose, 

 mannose or galactose (van Bruggen et al. 1943). It is noteworthy that a milk flavoprotein 

 has been described, whose antibacterial action also depends on its power to produce HgOg 

 from the medium containing the bacteria (Green and Pauh 1943). 



Penicidin. Penicidin is a relatively stable, diffusible substance, found in a number 

 of peniciUia, bactericidal for Salm. typhi at 1 : 100,000. Among the penicfllia so far tested, 

 there appears to be a negative association between the capacity to produce penicidin 

 and penicUlin-like substances. Penicidin activity, unhke that of penatin, is not sup- 

 pressed mider anaerobic conditions, but it is suppressed by — SH compounds (Atkuison 

 1942, 19436, Atkinson and Stanley 1943). 



Penicillic Acid. A chemically defined, water-soluble, aliphatic keto acid from Penicil- 

 Ikim cydopium. In the animal body it has about the same toxicity as phenol, but has 

 about 100 times as good an antibacterial action on Staph, aureus and Bad. coli, and it 

 may therefore prove to be chemotherapeuticaUy useful (Oxford, Raistrick and Smith 

 1942, Oxford 1942a). Peniciflic acid, and certain bacteriostatic quinones (see spinulosin, 

 below) are antagonized by peptone and certain amino-acids, as the result of combination 

 between the antibacterial agent and the antagonizer (Oxford 1942c). 



Penicillin. A water-soluble substance from P. notatum, active mainly against Gram- 

 positive bacteria (see below). 



Proactinomycin. A chemically undefined, relatively stable substance, from a Pro- 

 adinomyces. Bacteriostatic titres range from 1:1-5 x 10® for pneumococci, 1 : 5 X 10^ 

 for Staph, aureus and Str. pyogenes, to 1 : 2 x 10^ for Gram-negative intestinal bacflh. 

 It is more toxic than peniciUin to leucocytes (Gardner and Chain 1942). 



Spinulosin. A substance isolated from Penicillium spinulosum by Birkinshaw and 

 Raistrick (1931). It is a toluquinone, like fumigatin, differing from it only in possess- 

 ing an additional hydroxy group in the 6 position. It has the molecular structvu-e 

 3 : 6-dihydroxy-4-inethoxy-2 : 5-toluquinone. It is weakly antibacterial, and is chiefly 

 of interest in comparison with fumigatin, since the additional hydroxy group is associated 

 with a marked decrease in antibacterial activity (Oxford and Raistrick 1942). A study 

 of a number of toluquinones and benzoquinones revealed that the introduction of the 

 methoxy group OCH3 into the quuione often resulted in an increase, or of the hydroxy 

 group, in a decrease in activity. The substitution of the methoxy by hydroxy in an 

 active compound also decreased its activity (Oxford 19426). 



Streptomycin. A chemically undefined water-soluble substance from an unidentified 

 species of Adinomyces, apparently related to streptothricin. Like streptothricin, it acts 

 on Gram-negative and Gram-positive bacteria (Schatz, Bugie and Waksman 1944). 



