284 BACTERIOPHAGES 



had been replaced with bromine, iodine, or chlorine. For ex- 

 ample, T2 DNA, which normally contains 30 per cent thymine 

 among its bases, could be obtained with 6 per cent thymine and 

 24 per cent 5-bromouracil. The infectivity of such phage 

 progeny was measured in terms of optical density at 2,600 A per 

 plaque-forming particle (Chapter VII). Preparations were 

 obtained in which 50 to 90 per cent of the particles were non- 

 infective. Since the analogues were present before and after 

 infection it is reasonable to assume that all the phage particles, 

 infective or not, contained the unnatural base. Such prepara- 

 tions yield a high proportion of mutants (Litman and Pardee, 

 1956). It will be of interest to learn more about the properties 

 of these unnatural phage particles. 



Attempts to obtain similar incorporation of purine analogues 

 have been disappointing. Incorporation of 8-azaguanine into 

 the RNA of E. coli B, but not into bacterial or phage DNA, was 

 obtained by Lasnitzki (1954). A comprehensive discussion of 

 the incorporation of analogues into RNA and DNA may be 

 found in the review by Matthews and Smith (1955). 



Proteins may also be modified by replacing a natural amino 

 acid with its structural analogue. The incorporation of 7-aza- 

 tryptophan into bacterial and phage proteins was demonstrated 

 by Pardee, Shore, and Prestidge (1956). T2 produced after 

 infection in the presence of azatryptophan is noninfective and its 

 protein contains 0.4 per cent azatryptophan. Incorporation 

 was also obtained with tryptozan but not with 5-methyltrypto- 

 phan. 



6. Miscellaneous Inhibitors 



a. Antibioiics 



In the main, antibiotics prevent phage formation only to the 

 extent of their antibacterial properties. Like other metabolic 

 inhibitors they also may induce premature lysis, thus decreasing 

 the normal phage yield. As mentioned previously, penicillin 

 allows phage production under conditions which inhibit bac- 



