The replication process of bacteriophages can follow one of two ways; lytic or lysogenic. The differentiation of the two has been observed in the article Bacteriophage types – Replication cycles & Classification, however, the complexity of lysogeny, in particular, is an entire complex world of its own. This article will focus on the origins of the term and the discovery of the process.
Discovery of Lysogeny
In the short period between 1920 and 1950, crucial research and discoveries were made involving professionals from many divisions, which took a direct and an indirect approach towards the study of the nature and properties of bacteriophages. Lysogeny was one of the topics that was of concern to many. 490 articles were published between 1920 and 1940, of which 50 articles were about lysogeny. It is important to note that in the time the term ‘lysogeny’ was not as concretely defined as it is today. Many times, it was used in articles that had little to do with lysogeny. However, the heated interest on the topic created the foundation of the term today.
The main debate on the subject of lysogeny reached its peak between Felix d’Herelle, a Canadian known for the parallel discovery and naming of the bacteriophage, working at the Pasteur Institute in Paris, and Jules Bordet, Nobel laureate for his work in immunology and the director of Pasteur Institute in Brussels. D’Herelle viewed the bacteriophage as an ultra microbe that acts as a parasite towards bacteria. D’Herelle’s reasoning came from that he viewed the properties and replication of all phages as one, lytic, without taking into consideration the possibility lysogeny. Whilst Bordet denied such a view and considered that some strains of bacteria, which he called ‘lysogenic’, caused others to spontaneously go into the lytic cycle.
In an attempt to settle the dispute, Eugene Wollman from the Pasteur Institute in Paris, began extensive experiments to get to the bottom of the truth and became known to be one of the leading theorists on the topic. Amongst the many results he observed, his main view on the topic of lysogeny and phages was that there was an involvement of both vertical and horizontal transmission, which he referred to as ‘parahereditry’. After publishing six major memoirs with his findings, he also made a distinction that lysogeny seemed to be present in distinct species of bacteriophages. Unfortunately, Wollman’s research was interrupted by the end of 1943 due to the Nazis.
Lysogeny and Prophage
Between 1949 and 1952, Andre Lwoff a microbiologist and head of the department at the Pasteur Institute in Paris continued the work that Wollman began. Following and studying Eugene Wollman’s work throughout the years, he had a clear plan on where to continue. He concentrated on working with the B. megatherium strain, obtained from den Dooren de Jong, that Wollman worked with.
The bacteria they used were mostly free of virions and the following were their findings: approximately 1 phage per bacterium, came from 1 bacterium in 100 lysing and producing approximately 100 phages. This led him to the findings that the environmental factors played a role in how a bacteriophage chose to react. After experimenting with several stressors, he discovered that UV was one of the stressors that induced the entire culture to undergo lysis. This experiment was not only proof that phage-free bacteria could produce phages, but also set the term lysogeny into concrete terms.
Lwoff and his colleagues continued the research, which led them to the establishment of the term ‘prophage’ which they used to refer to a temperate phage and other viruses, which exist without virions or a phage protein. Prophage was later discovered to be the genetic material of a bacteriophage that incorporates itself into the bacteria’s chromosome. The term lysogeny was used towards bacteria, referring to lysogenic bacteria; bacteria that contained phage genes which when activated or induced by a stressor, switched to the lytic cycle. This study has been carried forward to this day and is known as the prophage induction.
In 1951 Esther Miriam Zimmer Lederberg, a microbiologist from the University of Wisconsin discovered lambda. When studying E. Coli strain K-12 after ultraviolet irradiation. In 1961, Allan Campbell, a microbiologist, isolated mutations that were identified as genes that are responsible for a lytic cycle.
The bacteriophage lambda consists of an icosahedral head and tail. It has a protein shell with approximately 15 proteins that contain the encoded viral genome. Bacteriophage integration happens at a specific site with the presence of two proteins; bacterial IHF and phage Int. When bound at a specific site of the ring phage genome, resulting in the formation of an intasome. Phage lambda can develop along the lysogenic and lytic path, depending on the environment it finds itself in.
The lambda was one of the earliest models for the study of the physical nature of DNA and genes. It eventually greatly contributed to the mapping of DNA and complete nucleotide sequencing. The discovery and study of the lambda opened doors in several divisions, such as genetics, especially in genetic research, genetic engineering and the development of several techniques used in genetics today.
The discovery of lysogeny and all the discoveries that followed were remarkable back in their time. Taking into consideration that between 1920 till 1960, technology was nowhere close to giving the opportunities it does today. These discoveries were not only the foundations of terminology that are used today, but also brought to light endless opportunities that are being studied to this day.