166 THE ANTIBIOTICS 



this preparation was later named by Welsch (58) actinomycetin, but this 

 as well was not a true antibiotic and was shown by Welsch himself to con- 

 tain an enzyme, which he designated as actinozyme. 



The first true antibiotic from a culture of an actinomyces may, therefore, 

 be said to have been isolated in 1940. It was designated as actinomycin (56). 

 The first such antibiotic which possessed chemotherapeutic possibilities 

 was isolated in 1942 (57) and was designated as streptothricin; it was a 

 result of an extensive screening program on actinomycetes for the produc- 

 tion of antibiotics (55). The first actinomyces-produced antibiotic that 

 found application as a chemotherapeutic agent was streptomycin, isolated 

 in 1943 (44). 



Since then, hundreds of thousands of cultures have been isolated and 

 tested. Systematic studies have been made of the distribution of cultures 

 active against various groups of bacteria, fungi, and other microorganisms. 

 Burkholder (11), for example, reported results of studies on 7,369 cultures. 

 Of these, 1,869 inhibited the growth of Micrococcus pyogenes var. aureus, 

 when the agar streak method was used, 261 inhibited Escherichia coli, and 

 514 were antagonistic to Candida albicans. According to Waksman, Horn- 

 ing, Welsch, and Woodruff (54) 20.1 per cent of all isolated cultures were 

 highly antagonistic, 23.3 per cent had some activity, and 56.6 per cent were 

 inactive upon bacteria. In general, 15 to 60 per cent of cultures of actino- 

 mycetes isolated from different natural substrates show some antimicrobial 

 activity. 



When different media are used for testing purposes, totally different 

 results may be obtained. Uesaka (47) and others, for example, have found 

 that certain cultures show one type of activity by the agar-streak method 

 and another type when grown in liquid media. It must further be remem- 

 bered that cultures of Streptomyces frequently produce more than one 

 antibiotic substance. This greatly influences the problem of screening, espe- 

 cially when cultures of bacteria made resistant to particular antibiotics 

 are employed or when antibiotic-producing cultures are used as test or- 

 ganisms, as shown by Oki and Hata (41). 



Production of antibiotics is a strain characteristic rather than a species 

 characteristic. Hence, certain strains of a given organism may produce a 

 particular antibiotic and other strains may not. Moreover, some strains of 

 the same organism may produce one antibiotic and others another. This is 

 illustrated by Streptomyces griseus, of which some strains produce strep- 

 tomycin, others grisein or streptocin or candicidin, and still others no 

 antibiotic at all. The same culture may also produce more than one anti- 

 biotic, as in the case of some strains of S. griseus which produce strepto- 

 mycin and cycloheximide, or several forms of the same antibiotic, as 

 streptomycin and mannosidostreptomycin. 



