rH( )i)i(^'ri()\ OK wriBioTics 



235 



lioui's, when tlu> slope of the ciirNC (Iccicnscd 

 with :i tciulency to lo\"i'l ot'f. In all cases the 

 peak of tlie st reploinyciii eurx'e Iat;i!;e(l l)e- 

 hiiul the p(\-ik of the t^rowth eur\-e by about 

 24 hours. 'I'he eoiu-hision was nviched that 

 streptomycin prinhiction in \\\c nunliuni is 

 not primarily a function of tiie act i\'e ,i;i()\vtli 

 phase of N. (in'scus. Only al)out 25 to oO per 

 cent of the total streptomycin had l)e(>n re- 

 leasinl into tlie solution hy the time the 

 growth peak was reached. 



On continued growth in artihcial nuHha, 

 S. gi'iscus may become contaminated with a 

 phage or virus, designated as actinophage. 

 The growth of the streptomycin-producing 

 organism and th(^ prothiction of streptomy- 

 cin are rapidly cUminished. B}^ the use of 

 the placiue method, it is possible to measure 

 the actual concentrations of actinophage in 

 the culture. The number of particles per mil- 

 liliter can reach as high as 10'". Phage-resist- 

 ant strains can be readily obtained from in- 

 fected cultures. 



Streptomycin is a strong Ixise, belonging 

 to the glucosides, in which a diguanido-group 

 is linked to a nitrogen-containing disaccha- 

 ride-like compound. A molecular weight de- 

 termination on the trihydrochloride in water 

 ga\-e al)out 800 for the free base after the 

 necessar}' corrections for the chloride ion. 



Investigations carried out by Hunter et al. 

 on S. griseus with the aid of C^K)2 have 

 shown that the carbons of the guanidine side 

 chains in streptomycin are derived very 

 largely, and possibly entirely, from carbon 

 dioxide. The maximum incorporation of 

 C^Oo into streptomycin was between 0.4 and 

 O.o per cent. A much lower degree of fixation 

 of C'^ was obtained when no C^O-j was passed 

 for the hrst 72 hours of the fermentation. L- 

 arginine possibly functions as an intermedi- 

 ate in the biosynthesis of the guanidine side 

 chains of streptomycin. A variety of com- 

 pounds, either containing guanidine groups 

 or readily changed into such compounds, are 

 converted by *S'. griseus into a further sul)- 



stance containing at least one guanidine 

 group. This compound has not yet been iden- 

 tified l)ut may l)e invoh'cd in the biosynthe- 

 sis of st leptomycin by the organism. 



On catalytic hydrogenat ion of sln^ptomy- 

 cin, two hydrogen atoms are added to the 

 molecule, gix'ing dihydi'ost I'cptomycin. 



K(>cently it was i-eported that certain or- 

 ganisms (S. humiflNs) can produce dihydro- 

 streptomycin directly in the medium. This 

 product is similar to streptomycin in its anti- 

 bacterial and pharmacological j^rojK'rties, ex- 

 cept that in many cases it exerts a less severe 

 effect upon \'estibular dysfunction, although 

 it may give greater autotoxicity. These re- 

 sults so far have not been confirmed. 



Certain organisms belonging to the Strep- 

 tomyccs group also produce desoxy strepto- 

 mycin, which was found to be more toxic 

 than streptomycin. 



Streptomycin is active against a large 

 number of bacteria found among the gram- 

 negative, gram-positive, acid-fast, and spi- 

 rochaetal groups. Many of the bacteria af- 

 fected by streptomycin are able to cause a 

 great variety of human, animal, and plant 

 diseases. Streptomycin is also active against 

 certain plant-disease-producing fungi be- 

 longing to the phycomycetes. It is not active 

 against anaerobic bacteria, protozoa, vi- 

 ruses, and the majority of fungi. The sensi- 

 ti^'ity of a given organism to streptomycin 

 depends not only upon the species, but also 

 upon the strain, and upon the composition 

 of the medium in which it is tested. The bac- 

 teriostatic and bactericidal action of strepto- 

 mycin upon M. tuberculosis, the causative 

 agent of tuberculosis, is particularly signifi- 

 cant. It is actiA'e in a concentration of 0.05 to 

 0.4 Mg/nil. The bactericidal action also varies 

 with concentration and the length of contact 

 with streptomycin, 0.3 /zg exerting an effect 

 in 48 hours, and 20 fjig/m\ in 6 hours. 



Sensitive bacteria become more resistant 

 to streptomycin upon prolonged contact with 

 the antibiotic. This is of considerable theo- 



