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

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Title: 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. Int. J. Mol. Sci. 2025, 26 , 2914".
Authors: Rojero M; Department of Biochemistry and Structural Biology, UT Health, San Antonio, TX 78229, USA., Weaver-Rosen M; Department of Biochemistry and Structural Biology, UT Health, San Antonio, TX 78229, USA., Serwer P; Department of Biochemistry and Structural Biology, UT Health, San Antonio, TX 78229, USA.
Source: International journal of molecular sciences [Int J Mol Sci] 2025 Nov 27; Vol. 26 (23). Date of Electronic Publication: 2025 Nov 27.
Publication Type: Comment; Journal Article
Language: English
Journal Info: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms: Bacteriophages*/physiology , Endopeptidases*/metabolism , Bacteria*/virology, Phage Therapy ; Bacteriolysis ; Lysogeny
Abstract: 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).
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Substance Nomenclature: EC 3.4.99.- (endolysin)
EC 3.4.- (Endopeptidases)
Entry Date(s): Date Created: 20251211 Date Completed: 20251211 Latest Revision: 20251214
Update Code: 20251214
PubMed Central ID: PMC12691794
DOI: 10.3390/ijms262311468
PMID: 41373624
Database: MEDLINE
Description
Abstract: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).
ISSN:1422-0067
DOI:10.3390/ijms262311468