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. Int. J. Mol. Sci. 2025, 26, 2914.

Presented here are additional explanations for five key points offered by Rojero et al. in their 2025 publication in this journal, regarding characteristics of hyper-aggressive phage 0524phi7-1. These are (i) that the "bypassing of the evolution of host resistance" has been seen in other phages, especially dual-receptor generalist phages; (ii) that the "clearing of semi-turbid plaques" could be due to a phenomenon known as lysis inhibition collapse, (iii) that the "formation of satellite plaques" is reminiscent of the morphology of plaques generated by phage T4 star mutants, (iv) that "multi-day plaque enlargement" has been seen in other phages such as phage T7 but may also be explained by other phenomena including endolysin release, (v) that suggestions of phage "swimming" could be explained by virion diffusion within empty volumes found within maturing bacterial lawns. In particular, phage plaques that display lysis inhibition can influence the surrounding bacterial lawn well beyond their visible region. This presumably occurs via a reaction-diffusion mechanism whose leading edge of virion diffusion fails to display lysis inhibition, but which leaves in its wake lysis-inhibited bacterial infections that may not lyse in a timely manner. Phage-infected bacteria thus may be found well beyond a plaque's visible boundaries, along with diffusing endolysin.