Physical and chemical properties of a bacterial virus as related to its inhibition by streptomycin

Abstract

Streptomycin specifically and reversibly inhibits the injection mechanism of a bacterial virus (P9) which attacks Streptococcus faecium. Dihydrostreptomycin does not inhibit injection, but reverses the inhibition brought about by streptomycin. Another virus of this same host (P3) is resistant to inhibition, and it is also possible to isolate mutants of P9 which are partially resistant. Streptomycin, but not dihydrostreptomycin, is able to cross-link and precipitate polyanions, and it is likely that the cross-linking function of the antibiotic is involved in the inhibitory process. Evidence is presented that there is no marked difference in the DNA characteristics of the streptomycin-sensitive and streptomycin-resistant viruses. Indirect evidence from methylene blue-mediated photodynamic inactivation studies suggests that neither SM or DHSM penetrates to the DNA of the virus. Evidence from dark inactivation of the viruses by dyes or protamine sulfate, and its reversal by the antibiotics, suggests that the antibiotics combine in some way with the protein coat of both P3 and P9. Therefore resistance to SM 4 is not a consequence of inability to bind antibiotic. SM precipitates P3, probably by cross-linking between adjacent phage particles. SM does not precipitate P9, showing that the antiviral effect is not a consequence of interparticle precipitation. However, SM, but not DHSM, causes a marked increase in the sedimentation constant of P9 under conditions in which SM is biologically active. Under the same conditions SM, but not DHSM, causes a shrinkage of the head and tail of the phage particle as viewed under the electron microscope. It is postulated that SM causes a shrinkage of the phage particle by cross-linking between adjacent protein subunits of a single phage particle, and thus pulling the protein subunits closer together. Since SM, but not DHSM, causes both the shrinkage of the phage particle and the inhibition of injection, it is postulated that the inhibition of injection is a consequence of the ability of the antibiotic to cross-link the protein subunits of the virus particle. Neomycin, which is structurally unrelated to SM, but is an effective cross-linking agent, behaves in a manner similar to SM.