Thermal Inhibition of Phage Production in Mixture of Phage and Growing Susceptible Bacteria. ∗

Abstract

One of the most interesting aspects of the entire phage problem has been the question of how phage is formed. In earlier studies it appeared that phage was produced only in the presence of an actively growing bacterial substrate. This relationship found experimental verification in quantitative studies on the phage-bacterium reaction and led to the adoption of an equation in which phage production was expressed in terms of bacterial reproduction. 1 Further work, however, proved this relationship to be more apparent than real for it was found possible to impose conditions such that cell division was inhibited while phage continued to be developed at a very considerable rate. 2 , 3 , 4 The fact that phage can be produced at all in the absence of cellular reproduction indicated that the latter is not an essential conditioning factor for phage formation, even though the two phenomena ordinarily proceed concurrently and require careful adjustment of pH, temperature, electrolyte concentration, 5 , 6 etc., to be dissociated.

Attention was then devoted to the possibility that phage production might involve the autocatalytic transformation of an inactive precursor into phage. 7 Formal proof of the existence of the precursor in cell-free solution has not yet been obtained, although traces can be detected irregularly. 8 However, there is satisfactory evidence that the substance from which phage is developed exists within susceptible cells. 9 To demonstrate it, staphylococci are subjected to active growth in an oxygenated medium, after which they are washed and stored in Locke's solution at 5°C. These “activated” cells when mixed with phage in appropriate proportions, bring about a tenfold increase in phage titre within 2 minutes. 10