The adsorption of a phage to its host – often mediated by long tail fibers – is an essential step in phage infection. When studying adsorption of phages with two or more tail fibers, often, a significant fraction of the phage population tested does not bind to the host; this is called the residual fraction. In fact, a phage population can often be considered as heterogeneous – divided between phages that adsorb and phages that cannot adsorb to the host. The residual fraction– along with the burst size, the latent period, etc. – has a significant impact on the amplification of phages and the population dynamics during the infection process. We hypothesized that the residual fraction of phages with multiple tail fibers was the result of highly variable sequences in the genes coding for the tail fibers.

Sequential selection rounds were carried out to isolate the residual fractions and effectively binding fractions of phage T4 adsorbing to its host, Escherichia coli. In total 8 rounds of selection/amplification were performed, distancing the fractions by approximately 80 generations. Sequencing was performed on the genes coding for the proteins forming the phage long tail fibers. Significant variations were observed in gene 37, coding for the protein gp37 involved in host recognition.

Adsorption models were developed to account for the phage residual fraction resulting from these genetic variations. Agreement with data for both adsorption and population dynamics outperformed previous models. In addition, similar agreement was observed when testing other phages having two or more tail fibers, but not with phages having one or no tail fiber. This suggests that the high variability in tail fiber genes observed in phage T4 may also take place in other phages with multiple tail fibers.

These results can be used to improve phage performance in applications such as phage production and phage therapy.