Lessons I learnt from Phage Lambda
Lambda phage has played a significant role in my career. I started my research in University of Brussels with famous lambdologist Prof Rene Thomas who taught me bacterial genetics through creation of mutants. 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 Charonphage, I later used cI857 repressor of phage lambda to lyse E. colito release cloned cytoplasmic protein into medium for detection (first paper oncloning by our group from India, published in Gene ).
As a student, I was intrigued how viral infection was initiated through a binding process involving a specific interaction between lambda phage and the bacterial maltose pore LamB (lambdareceptor) and subsequent delivery of genome into the host E. coli cell. LamB receptor was 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 toa 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.
Interestingly as in lambda, SARS-CoV use spike protein to interact with ACE2 receptor fordelivery of viral RNA into the host cell. Mutations in spike protein could change the tropism of virus including new hosts or increase viral pathogenesisas has happened in the case of SARSCoV2. 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
