Lessons I learnt from Phage Lambda
Lambda phage has played a significant role in my career. I started my research in University of Bruxelles with famous lambdologist Prof Rene Thomas who taught me bacterial genetics done through creation of mutants. My work revolved around Escherichia coli DNA dependent RNA polymerase and its interaction with phage lambda. His lab introduced me to bacteriophage lambda and its genes. It was phage lambda which won me postdoc in US as my Professor needed someone who had worked with phage lambda to develop genomic libraries in Charon phage, I later used cI857 repressor of phage lambda to lyse E. coli to release cloned cytoplasmic protein into medium for its detection through interaction with antibodies present in the medium (first paper on cloning by our group from India, published in Gene ).
As a student in University of Bruxelles, I was intrigued how viral infection was initiated through specific interaction between lambda phage and the bacterial maltose pore LamB (lambda receptor) that led to delivery of phage genome into the host E. coli. LamB receptor was first identified by isolation of E. coli K12 mutants resistant to lambda phage. Then a mutant from lambda was isolated which could target alternate receptor. When phage cI26 (a strictly lytic derivative of lambda) was cultured with E. coli in conditions that suppressed the expression of lamb, mutant phage changed their specificity from LamB to a new receptor OmpF. Similarly other strains of lambda were identified which had an expanded receptor specificity and adsorbed to host cells more rapidly through isolation of simple genetic mutants. Mutations are easy to isolate in phages as they lack the proof reading activity.
It was interesting to discover the similarity with SARS-CoV virus which use spike protein to interact with ACE2 receptor for delivery of viral RNA into the host cell. Mutations in spike protein could change the tropism of virus including new hosts or increase viral pathogenesisas as happened in the case of SARSCoV2. Spike protein became a candidate for vaccine against SARS.
Is virus still evolving will depend how it will accumulate enough mutations to survive and recur every year like flu. Finally genetic mutants should become useful tools in understanding of spill over and tropism of these zoonotic viruses.
With Professor Rene Thomas