1950] GROWTH AND VARIATION OF BRUCELLA ABORTUS 299 



analogous to those used in the present study, these metabolites may prove to 

 have similar effects on population changes. For example, Dubos (1949) has re- 

 ported that virulent types of Mycobacterium tuberculosis are highly susceptible 

 to DL-alanine and serine, whereas avirulent variants are more resistant to these 

 amino acids; Dagley, Dawes, and Morrison (1950) determined with the help of 

 chromatography that certain amino acids, including alanine, accumulated when 

 E. coli was grown in a simple synthetic medium; Linggood and Woiwod (1949) 

 have described parallel increases between alanine accumulation and toxin pro- 

 duction in cultures of Corijnebacteriumdiphtheriae; and Gordon and Gordon 

 (1947) noted the development of alanine- and glycine-resistant strains of Shigella 

 dysenteriae. 



Finally, these results suggest the possibility of controlling population changes 

 of pathogenic bacteria within infected hosts, such as enhancing the establishment 

 of less virulent nonsmooth types in vivo through the administration of alanine, 

 which in turn may result in therapeutic effects. Studies in this direction are 

 now under way. 



SUMMARY 



The application of paper chromatography to studies of the growth and varia- 

 tion of smooth Brucella abortus in Gerhardt and Wilson's synthetic medium 

 revealed a striking correlation between the accumulation of certain amino acids 

 in the medium and the appearance of nonsmooth variants. 



The role of one of the amino acids, alanine, in favoring the establishment of 

 nonsmooth variants, was verified by the addition of filtrates of old cultures or 

 of alanine alone to freshly inoculated smooth cultures in synthetic medium. 

 Under both conditions, a more rapid and enhanced establishment of nonsmooth 

 variants was observed, and it was found that alanine markedly suppressed the 

 viable count of smooth cells but failed to exhibit a similar marked effect on 

 nonsmooth types. 



It thus appears that the accumulation of alanine as a metabolite of smooth 

 cells creates an environment favorable for the establishment of spontaneously 

 occurring nonsmooth variants. 



The possible metabolic pathways involved and the relation of these data to 

 general phenomena of population changes have been discussed. 



REFERENCES 



Bail, O. 1929 Ergebnisse experimenteller Populationsforschung. Z. Immunitats., 60, 



1-22. 

 Bkaun, W. 1946 Dissociation in Brucella abortus : a demonstration of the role of inherent 



and environmental factors in bacterial variation. J. Bact., 61, 327-349. 

 Braun, W. 1947a Bacterial dissociation. Bact. Revs., 11, 75-114. 

 Braun,W. 19476 The production of apparent cycles in bacterial variation. J. Bact., 53, 



250-251. 

 Braun, W. 1949 Studies on bacterial variation and selective environments. II. The 



effects of sera from Bruce^a-infected animals and from normal animals of different 



species upon the variation of Brucella abortus. J. Bact., 58, 299-305. 



141 



