ANTIBACTERIAL SUBSTANCES FROM MOULDS 177 



Aspergillic Acid. This acid has been isolated in crystalline form from Aspergillus 

 flaviis, and has a provisional formula C12H20N2O2. It is bacteriostatic and bactericidal 

 for a wide range of organisms, including both Gram-positive and Gram-negative species. 

 It is toxic for mice, and no therapeutic effect could be obtained in mice infected with 

 pneumococci or Str. pi/ogenes (White 1940, White and Hill 1943). Gram-positive bacteria 

 are more susceptible than Gram-negative bacteria. Thus Jones and his colleagues (1943) 

 inhibited 30 X 10® pneumococci with 4/ig of the acid, 5,000 CI. welchii with 40/ig, and only 

 500 Bad. coli with SO/iig. 



Citrinin. Citrinin is a chemically defined, yellow substance, readily obtainable in 

 large quantities from Penicillium citrinum (Hetherington and Raistrick 1931, Coyne, 

 Raistrick and Robinson 1931). It is inhibitory for Gram-positive bacteria and, to a lesser 

 extent, for Gram-negative bacteria (Oxford 1942a). 



Clavacin. (Claviformin, clavatin, patulin). Clavacin is a water-soluble, acidic sub- 

 stance from Aspergillus clavalus. It is bactericidal, moderately bacteriostatic in low 

 concentrations (1 : 50,000 to 1 : 500,000), and is active against Gram-positive and Gram- 

 negative bacteria. It is toxic to animals (Waksman, Horning and Spencer 1943). The 

 same substance was isolated from Penicillium claviforme as claviformin (Chain, Florey 

 and Jennings 1942) ; and from Penicillium patulum as patulin by Raistrick and his 

 colleagues (1943), who identified it as anhydro-3-liydroxymethylene-tetrahydro-y-pyrone- 

 2-carboxylic acid. They reported that its application to the nasopharyngeal mucosa of 

 man was beneficial in the treatment of the common cold. Stuart-Harris, Francis and 

 Stansfeld (1943) and Stansfeld, Francis and Stuart-Harris (1944) could not confirm this, 

 nor could a specially appointed Committee of the Medical Research Council (Report 1944). 

 A similar substance was obtained from Aspergillus clavatus (Bergel et al. 1943, Hooper 

 et al. 1944), and from Aspergillus giganteus (Florey et al. 1944). Chain, Florey and 

 Jennings (1944) identified claviformin with patulin, and found it to be more toxic to 

 leucocytes and tissues than to bacteria. Katzman and his colleagues (1944) confirm 

 the identity of clavacin and claviformin, while Waksman (1944) claims that fumigacin 

 and helvoUc acid (see below) are also identical with clavacin. 



Flavacin. A chemically undefined, organic acid from Aspergillus flavus, which is 

 bacteriostatic for Gram-positive bacteria, but has little eflfect on Gram-negative bacteria. 

 In purified preparations it is moderately toxic to mice ; and from limited experimental 

 tests appears to protect mice infected with Type I pneumococci (Bush and Goth 1943). 



Fumigacin. Fumigacin is a chemically undefined substance from Aspergillus fmni- 

 gatus, soluble in alcohol, sparingly soluble in water. It is active mainly against Gram- 

 positive bacteria, and is bacteriostatic in low, bactericidal in high concentrations ; it is 

 fairly toxic to animals (Waksman, Horning and Spencer 1943). 



Fumigatin. Fumigatin, first isolated from Aspergillus fumigatus by Anslow and 

 Raistrick (1938), has since been synthesized (Baker and Raistrick 1941). It is a quinone 

 with the molecular structure 3-hydroxy-4-methoxy-2 : 5-toluquinone. It is strongly anti- 

 bacterial, particularly against V. cholerce, B. anthracis and Staph, aureus (Oxford and 

 Raistrick 1942 ; see Spinulosin below). 



Gigantic Acid. An antibacterial substance of the penicillin type from Aspergillus 

 giganteus (Philpot 1943). 



Gliotoxin. A highly toxic, crystalline, sulphur-containing antifungal and antibacterial 

 substance, with a provisional formula Ci4Hi6N2S204, found in OUocladium fimhriatum and 

 certain other fungi (Weindling and Emerson 1936, Weindhng 1937, 1941, Waksman and 

 Woodruff 1942). 



Helvolic Acid. A crystalline substance, with a provisional formula O^^^n^a^ from 

 a variety of Aspergillus fumigatus. It has little action on Gram-negative bacteria, but 

 inhibits Gram-positive cocci and Clostridia in high dilution. Bacteria become resistant 

 by serial subculture in media containing low concentrations of the acid. Its activity is 

 not markedly inhibited by blood or serum, and bacteriostatic concentrations are attained 

 in the animal body without untoward toxic effects. 



