272 A MANUAL OF THE ASPERGILLI 



A more detailed study of this strain was subsequently made by White and 

 Hill (1943) and the name "aspergillic acid" was assigned to the active 

 substance. The compound shows a comparatively high toxicity to labora- 

 tory animals. Utilizing the White strain, Jones, Rake, and Hamre (1943) 

 have made additional studies on the biological properties of aspergillic acid. 

 In the meantime, Glister (1941), at Oxford University reported the produc- 

 tion of an antibacterial substance effective against gram-negative and 

 gram -positive bacteria by a different strain of A . flavus (found by the writers 

 to be wholly typical of the species). He noted the possibility of relationship 

 between the substance with which he was working and that earlier reported 

 by White. 



Following the work of Jones, Rake, and Hamre (1943), McKee and Mac- 

 Phillamy (1943) succeeded in demonstrating the production of a second and 

 entirely different antibacterial substance. In certain chemical properties, 

 and in its action on bacteria, this was found to resemble penicillin very 

 closely, but actual identity was not proved. In a subsequent and more 

 detailed report, McKee, Rake, and Houck (1944) defined more exactly its 

 bactericidal action against various gram-negative and gram-positive bac- 

 teria and proved additional evidence of its penicillin-like characters. They 

 designated the substance i ''flavicidin'". 



Concurrent with this work, Bush and Goth (1943a and 1943b), working 

 at Vanderbilt University, succeeded in demonstrating the production of an 

 antibacterial substance from still another strain of A. flavus which was 

 strongly active against Staphylococcus and other gram -positive forms but 

 comparatively inactive against gram-negative forms belonging to the E. 

 coli group. The substance was termed "flavicin". Identity with flavicidin 

 and with penicillin is possible but has not yet been proved. Cook and 

 Lacey (1944) report the production of appreciable amounts of an antibiotic 

 substance from a strain of A. parasiticus. This was provisionally desig- 

 nated "parasiticin", and its similarity to penicillin was noted. Identity 

 with flavicin (Bush and Goth) and flavicidin (McKee, Rake, and Houck) 

 was suggested. Since A. parasiticus is so closely related to A. flavus, it 

 would seem probable that an antibiotic produced by it would be similar to 

 that produced by the latter species under the same conditions. 



Waksman and Bugie (1943) investigated a large number of strains be- 

 longing to the A. flavus-oryzae group. They found strains of A. oryzae to 

 show little activity, whereas strains of A. flavus showed increased but vary- 

 ing amounts. Yields' were markedly influenced by various nutritional and 

 environmental factors. Two types Of antibacterial substances were ob- 

 served: aspergillic acid and a substance similar to, if not identical with, 

 penicillin. When grown in submerged culture, one strain was found to 

 produce amounts comparable to the best strains of Penicillium notatum 

 tested. Unfortunately, yields were not quantitatively determined. 



