322 MUTATION AND PLANT BREEDING 



A strain improvement program following this principle has been 

 carried out by the author and associates. The highest yielding strain 

 derived through a linear sequence of mutagenic treatments from the 

 original erythromycin-producing isolate of Streptomyces erythreus 

 (81) was selected as one parent. Other erythromycin-producing strains 

 of differing geographic origin, morphology, physiology, and levels of 

 synthesis have occasionally been found by the new antibiotics screen- 

 ing program. A number of single and double auxotrophs were 

 selected in these strains. In addition, it was necessary to prove the 

 different strains were not mutually inhibitory due to cross-sensitivity 

 and production of temperate phage, bacteriocins, or other antibiotics. 

 Various genetic markers other than nutritional deficiency were used 

 as aids to the recovery of infrequent recombinant classes or for proof 

 of recombination. Interaction between strains, probably due to 

 heterokaryosis, but no formation of stable recombinants has been 

 found. 



Screening for New Antibiotics 



Lack of knowledge of the role of antibiotics in ecology, paths of 

 biosynthesis, and mode of action prevent a rational as opposed to an 

 accidental approach to uncovering new antibiotics. Resumes of 

 screening methods for soil microorganisms are given by Waksman 

 (110) in several of his books with extensive literature references. The 

 approach of present day screening programs is not very different from 

 that described eight years ago (87). An outline of a generalized screen 

 ing method will acquaint the reader with the procedure: 



(a) Soil samples are obtained from diverse sources and individual 

 organisms selected by plating suspensions on solid media. A pre- 

 liminary growth step, in selective liquid media, usually to sup- 

 press molds and bacteria and favor actinomycetes, is often used. 



(b) Individual organisms are grown in a variety of media favoring 

 antibiotic synthesis. 



(c) The spent culture media, sterilized, concentrated, or extracted, 

 are tested for antibiotic activity against a variety of bacteria and 

 molds, and possibly viruses and tumors (43, 108, 116). 



(d) Organisms producing activity in this initial screen are regrown 

 under a larger variety of conditions and the antibiotic categorized 

 by paper chromatography to determine whether it is known or 

 new. A disappointing feature of this method is not the rarity but 



