AxrAcoMS'iMc PH()i'i';i{'rii-;s 



'21!» 



;i\('i';iu;c, "J") |)(M' cent of the i>(>l;ilcs wci'c 

 found to i)ro(lu{'(> an ant il)iotic. Ajjproxi- 

 matoly !l() p(>r (-(Mil of all lh(> antil)ioti('-pro- 

 (lucinii cultures foiincd si rcpiot luiciii oi' 

 (•los(>iy iTJatcd ('onii)ouiids. A half of the 

 fcMiiaindcr pfoduccHJ st rcptonixciii, ouc-t liiid 

 (of the other halfi formed let i-aeyelines. 

 Finally, most of thos(> that remained could 

 he identified witli on(> of the x-arious anti- 

 biotics which ha\'e heeii isolated from cul- 

 tiu'es of streptomyc(Hes. In other words, 

 2,250 cultures <>;a\-e strei:)tothricin-like anti- 

 liiotics, about 12.") streptomycin, 40 yielded 

 tetracyclines, oo produced other i)re\-iously 

 described antibiotics, and only oO yielded 

 new antibiotics. 



Test Organisms 



A wide selection of organisms is commonly 

 used in testing cultures for antibiotic ac- 

 tivity. Freciuently, a highly sensitive or- 

 ganism like B. subtilis or Staph, anreus is 

 u.sed. In a search for a specific antibiotic 

 against a particular parasite, such as AI. 

 tufx-rrxlosis^ the latter itself or a form closely 

 related to it is used as the test organism. In 

 most cases, however, \-arious organisms are 

 used, including gram-positive and gram- 

 negative Ixicteria, saprophytic and parasitic 

 fungi. Plate method techni(iues have been 

 developed by Waksman and Reilly (1945), 

 Waksman et al. (1947), and Williston ef al. 

 (1947). 



Recently, actinomycetes possessing ac- 

 tivity against viruses and experimental 

 cancers have been investigated. For this 

 purpcse, special procedures are used, such as 

 tho.se involving bacteriophages (Jones and 

 Schatz; Schatz and Plager, 1948). Out of 

 527 cultures of actinomycetes screened by 

 Landerkin et al. (1957) for antiphage ac- 

 tivity, eight inhibited the development of 

 bacteriophages; of these eight, only one had 

 an elTect upon phages of two species of bac- 

 teria. None of the cultures tested had any 

 effect upon the Xewcastle virus. 



Ki'assihiikov and Kolano\a reported that 

 neai'ly all act inom^'cetes possess antiphage 

 properties. Some inhibit many phages and 

 others are elTectixc onl\- upon specific phages. 

 Actinomycetes show ;i characteristic anti- 

 l>hage spectrum. There is no relation between 

 aiiti\irus nnd antiphage antibiotics; there- 

 fore, tlu^ lattei- cannot be used as models for 

 study of antivirus agents. 



All iiitenssting in vitro techniciue utilizing 

 a modified agar plate diffusion method for 

 the detection of antitumor activity was 

 described by Miyamura. Ehrlich's ascites 

 tumor cells are incorporated into a ba.sal 

 medium. The materials to be tested are 

 placed in cups and allowed to diffuse through 

 the medium; the cups are then removed and 

 the plate is flooded with methylene blue; the 

 agar is covered with a glass plate and incu- 

 bated; the diameters of the blue zones are 

 measured. Positive results were obtained 

 with various anticancer agents including the 

 antibiotics trichomycin and sarkomycin and 

 8-azaguanine. Other antibiotics of actino- 

 mycetes (tetracyclines, streptomycin, and 

 neomycin) gave negative results. 



Aral and Suzuki published a modification 

 of the above method. Serial dilutions of the 

 materials to be tested are placed in tubes. 

 The tumor cells are added, the suspension is 

 mixed thoroughly, and then buffered glucose 

 agar containing methylene blue is added. 

 The results are read after 3 hours' incubation. 

 All antitumor substances tested, except 

 8-azaguanine, gave positive results. These 

 substances included sarkomycin, carzinoph- 

 ilin, the gancidin complex, and others. 



Rombouts (1953), Stevenson (1954), and 

 Links c/ a/. (1957) i.solated certain cultures of 

 streptomyces from soil that produced an 

 antibiotic possessing the capacity of causing 

 the swelling of hyphae of se\-eral fungi. The 

 substance responsible for this swelling was 

 designated as the ''bulging factor." This sub- 

 stance, isolated from the medium, proved 

 to be a streptothricin-likc base readily solu- 



