Integrating Past and Present PHAGE Research

It is a pleasure to present the March 2026 issue of PHAGE.

As our need for phages becomes ever more apparent, it is increasingly clear that progress in phage biology and translation benefits from the strands of a clear historical perspective, a comprehensive mechanistic understanding, and on the learning what the factors are that allow practical translation. This issue brings together work that spans all three elements and illustrates how insights from the past and from fundamental biology continue to shape present and future uses of bacteriophages.

We open this issue with a thoughtful perspective article that returns us to the early conceptual foundations of phage research. The article by Andrey Leterov from the Winogradsky Institute of Microbiology in Moscow, on bacteriophage thinking in the USSR during the 1930s, introduces readers to the work of Professor M.I. Lurie, whose monograph on the Twort-d’Herelle phenomenon was published just before the Second World War but, in part due to this, subsequently faded from view. Revisiting these early attempts to conceptualize phages and their mechanisms is not simply a historical exercise. It reminds us that many of the questions that occupy the field today were already being actively debated nearly a century ago, often under far more challenging conditions!

The importance of understanding phages within complex biological systems is further reflected in the research article examining host phage dynamics in the upper respiratory tract of individuals infected with SARS-CoV-2. By analyzing phageome and microbiome profiles from symptomatic individuals and healthy controls, Siddharth Singh Tomar and colleagues from the Environmental Epidemiology and Pandemic Management Centre, Nagpur, India, demonstrate how viral infection is associated with marked changes in both bacterial and phage communities. The observed disruption of host phage interaction networks highlights the sensitivity of these systems and reinforces the need to consider phages as integral components of microbial ecology rather than isolated agents. Several articles in this issue address the practical challenge of controlling clinically relevant pathogens.

Two independent studies by Andrea Katherine Álvarez Osorio et al. and Lan Yang et al. from Universidad de los Andes and the Shanghai Institute of Phage, respectively, then focus on Klebsiella pneumoniae, which is a major cause of concern in health care settings due to its persistence on surfaces and because of its increasing virulence and resistance to antibiotics. The study by Álvarez Osorio explores the use of phages to reduce multidrug-resistant K. pneumoniae on common clinical materials, providing data that can inform future decontamination strategies, whereas the article by Yang characterizes a novel lytic phage with tail-associated depolymerase activity targeting carbapenem-resistant strains. This highlights the potential of phage-encoded enzymes as adjuncts or indeed alternatives to whole phage therapy.

Mechanistic insights are of course central to our field, and this issue includes both a detailed review and original research focused on phage-mediated lysis. The review by Zahra Nasiri Shoeibi from Tehran University of Medical Sciences, on holins and spanins, summarizes our current understanding of the tightly regulated lysis proteins and outlines emerging applications that extend beyond bacterial killing. The research article by Prasanth Manohar and Ry Young from Texas A&M University provides a revised analysis of the lysis genes of the model phage SP6, where careful re-annotation and experimental validation together correct long-standing inaccuracies in order to clarify the lysis gene organization across a wider phage family. Together, these contributions highlight the value of revisiting well-studied systems both with modern tools and fresh perspectives.

Broader perspectives on phage therapy are provided by a comprehensive review by Mohammed Imam from the Department of Medical Microbiology and Parasitology at Al-Qunfudah, Umm Al-Qura University, Saudi Arabia, who examines the challenges that continue to limit wider clinical implementation and highlights potential solutions. Regulatory frameworks, safety considerations, delivery, and resistance are discussed alongside recent advances in genomics and engineering. Rather than offering simple solutions, the review underscores the need for coordinated progress across disciplines if phage therapy is to move from individual successes toward routine clinical use.

As always, we are very pleased to include bacteriophage introductions that expand the known diversity of phages and drive their potential for new applications. This issue features a phage isolated by Ruth Antoinette D. Chin from De La Salle University Dasmariñas, from rice paddies in the Philippines, with potential as a biocontrol agent against bacterial leaf blight in rice (caused by Xanthomonas oryzae), as well as work by Paul Nicholls et al. from Baylor College of Medicine, Texas, that describes the characterization of a genetically distinct Pseudomonas phage that challenges standard bioinformatic predictions of lifestyle. These studies highlight both the global nature of phage discovery and the importance of combining genomic analysis with experimental validation.

In brief, we very much hope that readers will find this issue informative and thought-provoking. Somehow, it exemplifies how progress in phage research often emerges from careful integration of history, mechanism, and application. As always, we thank our authors, reviewers, and readers for their continued support of PHAGE and for contributing to the field of phage research that you are helping to bring to life and evolve in exciting and productive ways.

With best wishes,

Martha Clokie and Thomas Sicheritz-Pontén