Chapter 9 



Modes of Action of Antibiotics 



Ehilich defined chemotherapeutics as 

 substances which are bound directly to 

 pathogenic microbial cells, damaging the 

 micro])e without affecting the host. At first 

 this concept was not generally accepted. The 

 prevailing idea was that the action of chemo- 

 therapeutic agents consisted in stimulating 

 the body defenses against the invading mi- 

 crobes. Later this idea appeared to be sup- 

 ported by the demonstration that prontosil 

 was effective in vivo but not in vitro. Ehr- 

 lich's concept was fully substantiated only 

 when it was established that the acti\'e sub- 

 stance in prontosil was sulfanilamide, which 

 w^as split off in the body, and that this 

 substance was active both in vitro and in 

 vivo. The action of antibiotics upon patho- 

 genic organisms served to support this idea 

 further, thus contributing materially to the 

 rapid progress in the utilization of antibiot- 

 ics as chemotherapeutic agents. Some in- 

 vestigators went even further in suggesting 

 that, since the activity of therapeutic agents 

 upon microbes consists largely in their effect 

 upon microbial metabolism, all substances 

 which have such an effect should be con- 

 sidered as antibiotics (Ericsson and Svartz- 

 Malmberg, 1959). Such a concept is scarcely 

 justified, however, since all sorts of com- 

 plexes, both of natural origin and syntheti- 

 cally produced, have therapeutic poten- 

 tialities. 



We still know relatively little concerning 

 the mechanisms involved in the selective 

 action of antibiotics upon different bacteria 

 and other microorganisms. This phenome- 



non cannot be correlated with either the 

 morphological or staining properties of the 

 sensitive organisms. True, some antibiotics 

 are active largely upon bacteria and others 

 upon fungi or animal forms, such as amoebae 

 and trypanosomes, luit the differences in 

 their action are so marked that no broad 

 generalizations can yet be made. 



Alost investigators have emphasized the 

 modes of action of clinically useful anti- 

 biotics. Some (Lardy ci a/., 1908) described 

 the action of antibiotics which for various 

 reasons are not useful therapeutically, espe- 

 cially when considered as potential anti- 

 tumor agents. 



Numerous theories ha^•e been proposed to 

 explain the modes of action of antibiotics. 

 This action has been attributed to the fol- 

 lowing phenomena : 



1. The antibiotic interferes with microbial 

 cell division, thus preventing further growth 

 of the organism. The cell, unable to divide, 

 gradually dies. 



2. The antibiotic interferes with the meta- 

 bolic processes of the microbial cells by 

 substituting for one of the essential nutrients. 

 A specific inhibitory effect may be exerted 

 by those substances that are structuralh- 

 related to normal cell metabolites. Such 

 substances are taken up by the cell in com- 

 petition with normal nutrients. Since they 

 are useless to the cell for further reactions, 

 they block the process of growth. 



3. The antibiotic interferes with various 

 enzymatic systems, such as the respiratory 

 mechanism of the microbial cell, especially 



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