Double Whammy: Lysogenic Conversion

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In the early 1950s, UW researcher V. J. Freeman, working in the UW Department of Public Health, noticed an unusual result. He took a non-virulent strain of diphtheria bacteria (one that did not cause disease), exposed it to a specific bacterial virus, and found that he produced a virulent strain of the organism capable of causing disease. These virulent strains now had the ability to produce diphtheria toxin, the lethal factor in the disease; and simultaneously, they had become carriers of the infecting bacterial virus known also as bacteriophage, or phage.

UW microbiology professor Neal Groman went on to understand the mechanism of this conversion to virulence. When the effects of phage were first observed, it wasn't clear whether phage selected some pre-existing virulent mutants of the diphtheria bacteria, or directly induced the change to virulence.

Groman and his student colleagues demonstrated that the latter mechanism was responsible for the conversion to virulence. They showed that the gene for diphtheria toxin was part of the phage DNA. On entering the bacterial cells, the infecting phage DNA insinuated itself into the bacterial DNA, and this new genetic entity produced diphtheria toxin. These findings were confirmed when they found that excision of the phage DNA by artificial or natural means restored the bacterium to its former innocuous state.

The process by which a virus induces change in the characteristics of a bacterial host was named lysogenic conversion. Different phages bring about different conversions, but those that render their host pathogenic have received particular scrutiny.

Lysogenic conversion is involved in scarlet fever, and in some botulinum and staphylococcal toxins responsible for food poisoning.

The work with diphtheria revealed the importance of bacterial viruses in disease production and in the epidemiology of infectious diseases. Infectious outbreaks may be caused by the spread of a particular phage rather than by the spread of the bacteria themselves. In fact, that scenario is implicated in a recent diphtheria outbreak.footnote 1 But there is a silver lining to this cloud: the same phages may serve as markers to track and study epidemics.

  1. "Toxin Gene Carriage by Bacteriophages in Medically Important Bacteria," N. P. Cianciotto, Clinical Microbiology Newsletter, 8, 1 (1986).

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