On variants of B. pestis caviae resistant to lysis by the bacteriophage

In preliminary experiments last year we found that bacteriophage therapy did not influence the course of experimental mouse typhoid, produced by the feeding of B. pestis caviæ to mice. We were led, therefore, to inquire into the tendency of this organism to develop resistance to lysis, and to compare the virulence of such resistant strains with that of the original culture.

It was found that therapeutic administration of bacteriophage did not lead to production of resistants in vivo during the ten days period. Nevertheless, the mortality of animals treated during this period was the same as that among the untreated, infected controls.

Moreover, when the resistants were produced from the culture of B. pestis cavia in vitro, it was found that such resistants are avirulent. When fed to or injected into mice these resistants did not recover their susceptibility to lysis, and when recovered from animals killed for this purpose they were found to remain resistant and avirulent.

These findings indicate, therefore, that the failure of bacteriophage therapy in experimental mouse typhoid is due not to production of resistants, but to failure on the part of the bacteriophage to destroy all the susceptible bacteria.

It was found that resistants isolated from the lysed cultures of B. pestis caviæ maintained their resistance to lysis during twentyfive passages on agar, at frequent intervals. When transferred to broth, however, one group of resistants (namely, those which yielded an agglutinated growth upon first transfer to broth) became susceptible to lysis after 5 to 7 daily passages. The other group of resistants (yielding a diffuse growth in broth) failed to become susceptible to lysis even after 120 daily passages in broth.

Simultaneously with the recovery of susceptibility, the cultures of the first group regained the degree of virulence comparable to that of the parent culture of B. pestis caviæ.