​Lambda--E. coli co-evolution 

Bryan Andrews

Phages and bacteria engage in an evolutionary arms race centered at the interface between the phage tail fiber and the bacterial receptor. Bacterial phage-resistance variants arise quickly in phage-exposed populations, typically with alterations in, or loss of, surface receptors. Consequently, phages must rapidly adapt to use new receptors, either by restoring affinity to mutated receptors or by switching to orthologous receptors. Understanding these co-evolutionary dynamics will be critical in developing phage-based therapeutic applications.
 
To study this process, we use the well-studied systems of E. coli and phage λ, for which the relevant proteins are the E. coli surface receptor, maltoporin, and the λ tail fiber, J. We have generated libraries of J, containing >97% of the single-residue substitutions over a 150-residue domain known to interact with the bacterial surface. By selecting for rapid binding and high fitness, we can identify highly constrained sites, which may indicate functional residues.

In addition, a large subset of substitutions seems to increase fitness relative to wild type in our selections. We are especially interested in whether there is an association between such variants that rapidly bind the native receptor and variants that confer novel binding to alternative receptors. Toward this end, we are in the process of generating E. coli with novel receptors, representing hybrids between maltoporin and some of its orthologues and paralogs. By challenging λ to adapt to several of these novel receptors, we can evaluate the general mechanisms by which phage tail fibers overcome the problems presented by a rapidly evolving host.