WMMA'lIoNS, Ml TAI'loNS. WD A I )A I' T.VTK ».\S 



109 



ll(ti-\;ilh (n)")4) sujificstcd that, to va\so 

 the product i\(' capacity of cultiii'cs ol" Slrcp- 

 tonujccs of low aiitihiotic production, the 

 followiuij; tr(>atnuMits should he rcsoHcd to: 

 (a) uUraxiolct irradiation; (h) intcMisificatiou 

 of \itaiity l)y frc(|Ucut pa.ssagos; (c) i'cfriiz;ci-- 

 ation. riti'axiolct irrachation increased pro- 

 duction of tlie antihiotic hy 40 pei* cent. 

 I'"i'(M|Uenl passai;"es uiaxc .">() pci- cent hiiihei- 

 yields. No inij)ro\-enient was achie\ed hy 

 refriiieration. Spore formation on potato 

 l)locks was marked in the refrii!;erated 

 strains; none was ohserx'ed in tlie iri'adiated 

 ones or in those that had undergone fre- 

 (|Uent pas.sage. 



Mashima and Ikeda (1958) made a de- 

 tailed study of the effects of physical and 

 chemical agents upon induced mutations of 

 Strcptonu/ccs .species. I'ltraviolet light, x- 

 rays, and gamma rays effectively increased 

 the reverse mutation of the locus responsible 

 for methionine synthesis. X-rays and gamma 

 rays did not affect the reverse mutation rate 

 at the glutamate locus. A detailed study has 

 been made of the mutagenic activity of 4- 

 nitro(iuinoline-l -oxide, as shown in Table 17. 



Numerous other investigations have been 

 carried out on the \'ariability and mutability 

 of actinomycetes (Temple), especially in 

 connection with their antibiotic-producing 

 l)r()perties. 



Development of Resistance and Prob- 

 lems of Adaptation 



Microbial cells \-ary gi'eatly in their resist- 

 ance to\\ai'd their own metabolic products 

 and to various antirnici'ol)ial substances. The 

 action of bacteriostatic agents may consist 

 in the prolongation of the growth lag phase, 

 in the reduction of the general rate of growth, 

 or in hastening the rate of death of the bac- 

 teria; they may affect one stage or another 

 selectively. When organisms are allowed to 

 grow in the presence of an antimicrobial 

 agent, the concentration of the agent re- 

 (juired to bring about a gi\-en effect upon the 



Tahi.k 17 



Miildflinic (fftrt of Jf lulrofiiinioliiif loxnlc on the 



rcrrisr nnilolioii of ijl iiliiiiutlv locus (.Masliiiiiii 



and Ikcda) 



* The reverse mutant.s were counted on medium 

 I\', and the number of colonies at time on me- 

 dium II, 2.1 X 10", was taken as iho l)ase of cal- 

 cidatioii. 



t The actual number was li.O X 10"'. 



culture is gradually increased. This type of 

 adaptation may be nnersed when the cells 

 are again grown in a medium free from the 

 antibactei'ial agent; sometimes, this type of 

 adaptation may prove to be very persistent. 

 Adaptation of microorganisms to anti- 

 microbial agents has been explained as fol- 

 lows: 



1. Adaptation occurs l\v natural selection 

 from an initially heterogeneous population. 

 This theory has lost much support since 

 variations have been found to occur in 

 strains derived initially from a single cell. 



2. Adaptation occurs by actual modifica- 

 tion of the metabolism of individual cells. 

 This may l)e due to the establishment in the 

 cells of a mechanism alternative to that 

 normally in use, or to the (iuantitati\'e modi- 

 fication of existing mechanisms. 



3. The adaptation is due to a change in 

 some center of organization of the cell. 



The mechanism of accjuired drug resist- 

 ance may thus be due either to direct induc- 

 tion or to mutation with selection (Abra- 

 ham). The ease of de\'elopment of resistance 

 depends upon the oiganism and the anti- 

 microbial agent. In .some cases the organism 



