Reply to Abedon, S.T. Dual-Receptor Recognition, Lysis Inhibition, Endolysin Release, and Reaction-Diffusion as Alternative Explanations. Comment on "Rojero et al. Bypassing Evolution of Bacterial Resistance to Phages: The Example of Hyper-Aggressive Phage 0524phi7-1.

In this manuscript, we isolate and characterize a phage that displays what we call anti-bacterial hyper-aggressive behavior. This behavior appears ideal for phage therapy of bacterial disease. It includes (1) formation of semi-turbid zones that subsequently clear, (2) formation of miniature satellite plaques, which probably constitute the foundation of the semi-turbid zones, (3) multi-day enlargement of both circular plaques and cleared semi-turbid zones, and (4) non-formation of phage-resistant host colonies. We emphasize the following key details in our response. (1) The semi-turbid zones are asymmetric and occupy an area much larger (2-10x) than the area of circular plaques formed on the same Petri plate (unlike semi-turbid plaques associated with other phenomena, such as lysis inhibition and lysogeny). (2) In the manuscript's Figure 9d, we note that phage 0524phi7-1 destroys mature colonies of the host (unlike the behavior of other aggressive phages). (3) The asymmetry of semi-turbid zones is a point that we should have emphasized (because it implies non-diffusive, energy-requiring phage transport). (4) The input of energy for phage motion can be physical (to which we add some details for two physical effects); our mentioning of phage swimming is a hypothesis (that is, however, still viable).