NATURE OF ANTIBIOTIC SUBSTANCES 117 



can be replaced by starch, in which case the presence of agar is unneces- 

 sary. When grown in submerged or agitated cultures, the agar is left 

 out. The tryptone can be replaced by a variety of simple nitrogenous 

 compounds, such as glycine, alanine, aspartic acid, asparagine, and glu- 

 tamic acid (Table 22)} the carbohydrate may be left out completely, 

 with only limited reduction in activity. No growth of the organism is 

 obtained on tryptophane, phenyl alanine, and certain other forms of 

 nitrogen. With ammonium sulfate or sodium nitrate good growth may 

 be obtained but the production of the active substance is limited unless 

 the organism is grown under submerged conditions. Iron appears to 

 play an essential role in the production of the active substance. An in- 

 crease in growth as a result of an increase in carbohydrate concentration 

 does not result in an increase in streptothricin content, but an increase 

 in growth as a result of an increase in the amino-acid concentration, with 

 the same amount of carbohydrate, causes an increase in the production 

 of streptothricin. When the medium contains one amino acid as the only 

 source of carbon and nitrogen, there is a gradual increase in the alka- 

 linity of the medium, resulting in the destruction of the streptothricin. 

 Neither the growth of the organism nor the production of the strepto- 

 thricin, however, is influenced by the reaction of the medium, within 

 certain limits, even between /)H 4.4 and 8.0 (lOOi). The metabolism 

 of S. lavendulae and the course of production of streptothricin under 

 stationary and submerged conditions are illustrated in Figure 1 1 . Meth- 

 ods of isolation of streptothricin and its chemical properties are de- 

 scribed later (p. 173). Its bacteriostatic spectrum or action against vari- 

 ous bacteria is shown in Table 23. It has only limited toxicity to animals 

 and is active in vivo against both gram-positive and gram-negative bac- 

 teria (755). 



Certain strains of Streftomyces griseus produce an antibiotic sub- 

 stance, designated as streptomycin, that is also active against both gram- 

 positive and gram-negative bacteria. It is similar in its solubility and 

 various chemical properties to streptothricin j however, it acts readily 

 against B. mycoides and is more active than the latter against certain 

 gram-negative bacteria, such as Ps. aeruginosa. The organism grows 

 well in stationary liquid media containing meat extract or corn steep. 

 Streptomycin is active in vivo against a variety of bacteria, some of 



