236 



THE ACTIXOMYCETES, Vol. I 



retical and practical importance. Freshly 

 isolated cultures of tubercle bacilli from pa- 

 tients with pulmonary tuberculosis are uni- 

 formly sensitive to streptomycin. When a 

 culture is exposed to streptomycin in rela- 

 tively low concentrations, growth of the mul- 

 tiplying cells is inhibited but not that of the 

 nonmultiplying cells. This resistance persists 

 for a considerable time and is not accom- 

 panied by a diminution in virulence. The 

 principal effects of streptomycin on the mor- 

 phology of this organism were a loss of acid- 

 fastness, an increase in granulation, and, in 

 highly bacteriostatic concentrations, a short- 

 ening of the rods. The development of resist- 

 ance of bacteria to streptomycin does not 

 usually result in increased resistance to syn- 

 thetic agents, such as INH and PAS, or to 

 other antibiotics, such as tetracyclines. 



Among the other problems bearing upon 

 the effect of streptomycin upon bacteria is 

 the development, among certain strains, of 

 dependence upon this antibiotic. This phe- 

 nomenon has highly interesting biochemical 

 and clinical potentialities. 



No attempt can be made here to review 

 the extensive literature that has accumulated 

 on the effectiveness and utilization of strep- 

 tomycin. Suffice to say that up to 1952 

 (Waksman) nearly 6,000 references had ac- 

 cumulated. A comprehensive summary was 

 presented in various publications (Waksman, 

 1949, 1951). 



Neomycin 



Waksman and Leche^'alier first isolated 

 neomycin, in 1949, from a culture of S. jra- 

 diae. Neomycin or closely related compounds 

 were also found to be produced by a number 

 of different oth(>r organisms, such as S. al- 

 bogriscolus (Benedict et al.) and »S'. kanamy- 

 ceticus (Takeuchi et al.). They are l)asic 

 compounds, with a broad antibiotic spec- 

 trum (Table 65). They are acti\'e against 

 streptomycin-resistant l)a('leria, including 

 the tuberculosis organism. They were later 



found to be a mixture of several closelj^ re- 

 lated compounds, all exerting antimicrobial 

 effects, thus suggesting the term "neomycin 

 complex" (Dutcher and Donin, Ford et al). 

 One fraction isolated from the complex, was a 

 basic, water-soluble, nitrogenous substance, 

 designated as neomycin A. It gave 1,700 di- 

 lution units/mg against B. subtilis, by plate 

 assay, but only 50 units/mg against E. coli, 

 by turbidimetric assay. Neomycin B and ne- 

 omycin C, two isomeric fractions, were found 

 to be the major constituents of neomycin 

 (Lechevalier, 1951; Dulmage, 1953; Prieto, 

 1955; Waksman, 1958). 



Vifjmycin and Other Polypeptides 



Viomycin was isolated simultaneously, in 

 1951, in several laboratories from cultures 

 described as S. puniceus, S. fioridae, and S. 

 califnrnicus (Finlay et al., Bartz et al.). All 

 of these cultures were later relegated by 

 Burkholder et al. to be S. griseus var. pur- 

 pureas. Viomycin was found to be a strong 

 basic polypeptide which, upon acid hydroly- 

 sis, yields carbon dioxide, ammonia, urea, 

 L-serinc, a-, /^-diaminopropionic acid, an un- 

 identified guanidine compound, and a basic 

 amino acid that has also been found in strep- 

 tothricin and streptolin (Haskell et al.). 

 Viomycin is active mainly against acid-fast 

 organisms but shows some activity against 

 gram-positive and gram-negative bacteria. 



Chloramphenicol 



Among the antibic^tics that have found ex- 

 tensive therapeutic applications is chloram- 

 phenicol, isolated in 1947 by l^^hrlich and by 

 Gottlieb et al., from a culture of an actino- 

 myces {S. venezuelac) . l^mezawa et al. iso- 

 lated another chloramphenicol-producing 

 culture which differed from»S. venezuelae and 

 to which the name S. omiyaensis was as- 

 signed. Chloramphenicol was the first anti- 

 biotic of anactinomycete to be synthesized. It 

 contains niti'ogtMi and chlorine. It is active 



