NATURE, FORMATION, AND ACTIVITIES 



develop i-apid resistance to some anti- 

 biotics and not to others, as in the case of 

 staphylococci versus streptococci to peni- 

 cillin? Why do the rates of development of 

 resistance differ for different antibiotics, as 

 in the mechanism of development of resist- 

 ance among sensitive bacteria to neomycin 

 versus streptomycin? 



Why do some bacteria produce strains 

 that become nutritionally dependent upon 

 certain antibiotics, such as streptomycin? 



Were answers found to these cjuestions, 

 one could go a long way in establishing the 

 correlation between chemical structure and 

 biological activity of the various antibiotics. 



Even if they cannot be answered at pres- 

 ent, advantage is taken of some of the 

 known properties of the antibiotics in clas- 

 sifying them, utihzing them, and suggesting 

 an interpretation of their possible mode of 

 action. These can be briefly listed as follows: 



1. The phenomena of resistance and of 

 sensitivity of microorganisms to various 

 antibiotics permit the recognition of certain 

 close relationships among such antibiotics, 

 if not in their chemical structure, at least 

 in their biological activity. Thus, it is pos- 

 sible to recognize the similarity among anti- 

 biotic preparations long before their chemi- 

 cal nature has been established. 



2. Although it is now fully recognized that 

 the modes of action of various antibiotics 

 differ, too little is still known about this 

 phase of antibiotic behavior to warrant 

 speculation upon any possible relationships 

 between structure and activity. 



3. The toxicity of antibiotics to animal 

 tissues is known to differ great l.y. This phe- 

 nomenon is of importance in any effort 

 to evaluate the practical potentialities of 

 antibiotics in disease control. The reasons 

 for it, however, remain obscure. Neomycin, 

 for example, was shown to have an effect in 

 the treatment of tuberculosis, but it has so 

 far not taken a significant place in the arma- 



mentarium of phthisiologists, largel}^ be- 

 cause of its injurious nephrotoxic and oto- 

 toxic effects when administered parenterally. 

 Different modes of administration or the 

 supplementation of certain nutritional fac- 

 tors may be the answer for the practical 

 utilization of this antibiotic. 



4. Although it has been assumed that 

 activities of antibiotics in vitro and in vivo 

 are parallel, there are certain instances in 

 which they are not. This is true, for exam- 

 ple, of cycloserine, an antibiotic found to be 

 more active against the tubercle bacillus 

 in vivo than in vitro. 



,'-). Finally, attention must be directed to 

 the facts that actinomycetes also produce 

 growth-promoting substances (B12), and that 

 some antibiotics, in limited concentrations, 

 may also exert a growth-promoting effect 

 upon ^'arious forms of life — a property of 

 certain antibiotics that has been taken ad- 

 vantage of in the feeding of poultry, swine, 

 and other animals. These properties tend to 

 complicate further our concept of the chemi- 

 cal structure and biological activity of anti- 

 biotics. 



The following illustrations will sufhce to 

 emphasize that certain changes in the chemi- 

 cal structure of the antibiotic molecule may 

 result in marked changes in its biological 

 activity: 



1. When streptomycin is changed chemi- 

 cally to dihydrostreptomycin, whereby the 

 carbonyl group in the central hexose unit is 

 reduced, the characteristic antibacterial 

 properties of the drug are retained, although 

 there is a change in the nature of its poten- 

 tial toxicity. On the other hand, the treat- 

 ment of streptomycin by such carbonyl 

 reagents as hydroxylamine brings about in- 

 activation of the drug. The replacement of 

 the CH:j group in the central hexose unit 

 (streptose) by CHoOH, to give hydroxy- 

 streptomycin, seems to increase the toxicity 



