Evidence for host-dependent modification and restriction of bacteriophage DNA in Mycobacterium tuberculosis

Wild isolates of Mycobacterium tuberculosis may be divided into the three internationally recognized phage types on the basis of susceptibility to mycobacteriophages DS6A, BK1 and D34. Strains of type A are lysed at high efficiency by DS6A only; type B is lysed by BK1 grown on Mycobacterium smegmatis ATCC607 and DS6A, while type C is lysed additionally by D34 grown on atypical Mycobacterium F130. Propagation of D34 on a C-strain (D34-C) or BK1 on a B-strain (BK1-B) has no effect on viral host-range. D34-C has an efficiency of plating (e.o.p.) of 10(-5) on type B strains and 10(-7) on A strains. BK1-B plates on A strains at an e.o.p. of 10(-5). BK1 recovered from and repropagated on an A strain (BK1-A) has an e.o.p. of 1-0 on strains of all classes. D34-B has an e.o.p. of 1-0 on strains of type B and C, while D34-A plates with high efficiency on types B and C and displayed an e.o.p. of 10(-4) on type A. Repropagation of these viruses on the M. tuberculosis strains originally lysed by them results in the restoration of their previous host range. Variations in plating efficiency cannot be explained by differences in viral absorption alone. These findings suggest that the three phage types of human tubercle bacilli are related by a hierarchical pattern of DNA restriction and modification in which the C pattern is included in the B, and both patterns are included in A-modified DNA. Viruses such as DS6A which are equally virulent for strains of all classes are not susceptible to host dependent restriction.