DIFFERENTIATION OF BACTERIA 259 



1. By natural selection from an initially heterogeneous population. This 



concept, however, has lost much support, since variations have been 

 found to occur in strains derived initially from a single cell. 



2. By actual modification of the individual cells. This may be due (a) to 



the establishment in the cells of a mechanism alternative to that 

 normally in use or (b) to the quantitative modification of existing 

 mechanisms. 



3. By a change in some center of organization of the cell. 



Demerec (177) suggested that the development of strains of S. au- 

 reus resistant to penicillin is due to the formation of mutants, the non- 

 resistant cells being eliminated by the penicillin. The degree of resist- 

 ance can be increased by exposure to larger doses of the antibiotic j this 

 increase was considered to be a summation of several independent ge- 

 netic factors for resistance which undergo considerable mutation. Re- 

 sistant strains retained that property after many transfers. 



There are apparently several mechanisms whereby organisms such 

 as staphylococci develop resistance to penicillin. One consists in the de- 

 velopment of a penicillin inhibitory in other cases, however, no inhibitor 

 can be demonstrated (717). 



The adaptation of staphylococci to mycophenolic acid is not an easily 

 reversible phenomenon, thus suggesting that the adaptation consists in 

 the development of an alternative mode of growth, comprising a modi- 

 fication of the enzyme systems of the bacteria (2). The ending of the 

 lag of growth of S. aureus is due to a diffusible growth intermediate 

 produced by the cells j the primary action of the antibiotic consists 

 partly in hindering the utilization of this substance. The effect of the 

 antibiotic consists in a failure of the dividing cells to separate in the 

 normal manner. These changes do not occur in "trained" cells. 



DIFFERENTIATION OF BACTERIA BY MEANS 

 OF ANTIBIOTIC SUBSTANCES 



Because of their selective action upon different bacteria, antibiotic 

 substances can be utilized for separating bacteria from one another. 

 Fleming (264) utilized penicillin to isolate Pfeiffer's bacillus and the 

 pertussis organism of various cocci, diphtheria, and neisseria organisms j 



