devp:lopment of resistance 



107 



of organisms by the principle of survival of 

 the fittest. These investigators considered 

 the changes leading to the development of 

 resistance not as primarily drug-induced but 

 rather as a result of spontaneously occurring 

 mutations, leading to modified biochemical 

 processes in the bacterial cell and thereby 

 yielding resistant strains. Two types of 

 resistance were recognized: natural and 

 acquired. The first occurs in a natural popu- 

 lation, among species or sti'ains that have 

 had no previous contact with a given anti- 

 biotic (Table 36). The second takes place in 

 a bacterial population that has been in con- 

 tact with an antibiotic; resistant cells emerge 

 from an originally sensitive population. 



The emergence of antibiotic resistance was 

 regarded as essentially a phenomenon of 

 adaptation, of which two categories were 

 recognized: (1) genetic adaptation, in which 

 resistant mutants overgrow the population 

 under the selective effect of the antil)iotic; 

 (2) physiological, or phenotypic, adaptation. 



in which cytoplasmic alterations (adaptive 

 enzyme formation) are induced by the anti- 

 biotic, so as to render some of the cells more 

 resistant without affecting the genetic ap- 

 paratus (see also Garrod, IQ.IO). 



Some organisms, including resistant 

 species and naturally resistant strains, were 

 belie\'ed to possess cytochemical systems 

 that are not vulnerable to specific anti- 

 biotics. Degrees of resistance and sensitivity 

 were considered as relative. Two resistance 

 patterns were recognized: (1) the penicillin 

 or obligatory multistep pattern; (2) the 

 streptomycin or facultative one-step pattern. 

 The nature of the pattern permits prediction 

 of the pro})al)ility that resistance will develop 

 rapidly. Mutations to antibiotic I'esistance 

 were beliex'ed to include a wide variety of 

 types. Gain or loss of resistance, once muta- 

 tions to resistance have occurred, depends 

 primarily on selection, the presence or 

 absence of antibiotics playing a major part 

 (Bryson and Demerec, 1955). 



Table 36 



Approximate concentration required to produce detectable inhibition of cells in streaks of representative 



bacterial species on gradient plates (Brj'son and Demerec, 1955) 



