Abstract
The renewed interest in bacteriophage therapy as a response to antimicrobial resistance (AMR) has exposed a critical barrier to its scalable implementation: the lack of structured infrastructure to support precision phage deployment. Due to their narrow host specificity, bacteriophages require timely access to well-matched candidates, making ad hoc isolation and informal exchange insufficient for routine therapeutic use. In this Perspective, we argue that phage biobanks must be redefined as enabling infrastructure rather than passive repositories. We propose that next-generation phage biobanks should integrate curated biological diversity, systematic genomic and functional qualification, and predictive capacity to support rapid phage–host matching. Together, these elements transform biobanks into decision-support systems capable of informing translational applications under time-sensitive conditions. This infrastructural model is particularly relevant within a One Health framework, where resistant pathogens circulate across human, veterinary, agricultural, and environmental domains. Rather than reviewing methodologies, we outline conceptual principles to guide the design of phage biobanks as integrated, predictive, and sustainable assets. We contend that the future impact of phage therapy will depend less on individual phage discovery than on the development of interoperable biobank infrastructures that enable precision antimicrobial interventions at scale.
1 Introduction – why infrastructure, not collections
The global escalation of antimicrobial resistance (AMR) has reopened the therapeutic landscape to alternatives and complementary strategies beyond conventional antibiotics, placing bacteriophages back into focus as precision antibacterial agents that can be deployed alone or in combination with existing antimicrobial therapies (Garvey, 2020). Unlike small-molecule antimicrobials, bacteriophages exhibit a high degree of host specificity, often acting at the level of bacterial species, subspecies, or even individual strains (Peng et al., 2025). This biological property, while advantageous in terms of selectivity and microbiome preservation, introduces a fundamental structural challenge for the deployment of phage therapy at scale: effective treatment depends on timely access to phages that match the infecting bacterial isolate.
To date, much of clinical and experimental phage therapy has relied on ad hoc strategies, including bespoke phage isolation, informal inter-laboratory exchanges, or emergency compassionate-use networks (Jones et al., 2023; Niazi, 2025). Although these approaches have enabled remarkable individual successes, they remain inherently reactive, fragmented, and poorly scalable. In this context, the absence of organized, interoperable phage biobanks represents a critical bottleneck for the broader translation of phage therapy into routine clinical, veterinary, and agricultural practice (Zalewska-Piątek, 2023).
Phage biobanks are often discussed as repositories of biological material; however, such a definition underestimates their strategic role. In the AMR era, phage biobanks should be understood as enabling infrastructure: systems designed to support rapid decision-making, quality assurance, and translational deployment of phage therapeutics (Lin et al., 2021). Their function extends beyond storage to include the curation of biological diversity, the integration of genomic and functional information, and the facilitation of phage–host matching under time-sensitive conditions. This infrastructural perspective is particularly relevant in a One Health framework, where resistant bacterial pathogens circulate across human, animal, agricultural, and environmental interfaces (Samson et al., 2024). A biobank capable of supporting precision phage therapy in one sector can, if properly designed, serve multiple domains simultaneously. Thus, phage biobanks occupy a unique position at the intersection of microbiology, data science, and translational medicine.
In this Perspective, we argue that the future success of phage therapy depends not primarily on the discovery of individual “ideal” phages, but on the development of phage biobanks as integrated, predictive, and interoperable infrastructure. Rather than providing an exhaustive review of methodologies, we focus on the conceptual principles that should guide the design and function of next-generation phage biobanks, positioning them as foundational tools for precision antimicrobial therapy.
2 Host specificity as the architectural constraint
The defining biological feature of bacteriophages (their narrow host specificity) constitutes the primary architectural constraint shaping the design of phage biobanks. Unlike antibiotics, whose activity often spans multiple species or genera, most phages infect only a limited subset of bacterial strains. This specificity underpins the precision of phage therapy but simultaneously precludes universal or “one-size-fits-all” therapeutic solutions (Jones et al., 2023).
From an infrastructural standpoint, host specificity transforms phage therapy from a problem of drug availability into a problem of matching. Effective deployment depends not on the existence of a single highly potent phage, but on access to a sufficiently diverse repertoire capable of covering the genetic and phenotypic heterogeneity of target bacterial populations (Strathdee et al., 2023). Consequently, phage biobanks must be designed around diversity, redundancy, and continuous expansion, rather than around a fixed or finite collection.
This constraint has direct implications for how biobanks define their scope. Species-level representation is insufficient; clinically and environmentally relevant variation often occurs at the strain level, driven by differences in surface receptors, mobile genetic elements, and resistance mechanisms (Egido et al., 2022). A biobank optimized for precision therapy must therefore prioritize depth within high-priority bacterial taxa, rather than breadth across unrelated organisms (Kaur et al., 2021). In this sense, the value of a phage biobank is not measured by the absolute number of phages it contains, but by how effectively its collection maps onto the diversity of circulating bacterial hosts.
Host specificity also imposes temporal constraints. Bacterial populations evolve rapidly, particularly under antimicrobial pressure, leading to shifts in susceptibility profiles and receptor usage (Zhao et al., 2024). Static collections risk obsolescence unless they are continuously refreshed and re-evaluated. Phage biobanks must therefore be conceived as dynamic infrastructures, capable of adapting to changing bacterial landscapes rather than preserving historical snapshots of phage diversity (Resch et al., 2024). Importantly, host specificity should not be viewed as a limitation to overcome, but as a design principle to embrace. When properly leveraged, it enables targeted interventions that minimize off-target effects and preserve beneficial microbiota (Cui et al., 2024). However, realizing this advantage at scale requires biobanks that are explicitly structured to accommodate specificity through strategic collection growth, curated host coverage, and integration with downstream qualification and matching processes. In this framework, host specificity is not merely a biological characteristic of phages; it is the organizing logic around which effective phage biobanks must be built.
3 From isolation to qualification: making phages “bankable”
The transition from individual phage isolates to functional elements of a biobank requires a conceptual shift from discovery to qualification. In the context of precision phage therapy, not every isolated phage is suitable for inclusion in a biobank. Instead, phages must undergo a process of biological, informational, and externally anchored validation that renders them bankable: safe, interpretable, and deployable within a therapeutic pipeline (Panagiotopoulos et al., 2025). This qualification process extends beyond internal laboratory characterization and increasingly aligns with independent quality frameworks, including those articulated in the European Pharmacopoeia General Chapter 5.31 for phage therapy medicinal products, which define reference expectations for identity, genomic integrity, purity, and safety (European Directorate for the Quality of Medicines & HealthCare of the Council of Europe (EDQM), 2024). In this sense, “bankability” reflects not only scientific suitability, but compatibility with externally recognizable standards that support translational use.
At this stage, isolation alone is insufficient. While environmental and clinical sampling continue to expand the known diversity of bacteriophages, the translational value of these discoveries depends on their systematic qualification. Phage biobanks therefore operate not as passive repositories of isolates, but as curated systems that apply defined inclusion criteria (Xing et al., 2025). Central to this process is genomic qualification, which serves as the primary gatekeeper for biobank entry (Calero-Cáceres and Balcázar, 2025). Whole-genome analysis allows the exclusion of phages carrying genes associated with lysogeny, virulence, or horizontal gene transfer, thereby aligning biobank contents with safety expectations for therapeutic use (Gholizadeh et al., 2024). Beyond safety, genomic characterization provides a stable reference framework for classification, traceability, and interoperability. In contrast to phenotypic assays that may vary with experimental conditions, genomic data constitute a reproducible and transferable layer of information that anchors each phage within the biobank (Banerjee et al., 2025). This genomic anchoring is essential for regulatory dialogue, inter-institutional exchange, and long-term collection management.
Functional qualification complements genomic screening by establishing the biological relevance of a phage within its intended context of use. Rather than exhaustive phenotyping, biobanks must define functional criteria that are directly aligned with translational objectives, such as demonstrable lytic activity against representative host strains or efficacy under conditions relevant to infection biology (Lin et al., 2021). Importantly, this functional layer is not designed to predict therapeutic outcomes in isolation, but to ensure that phages included in the biobank possess a minimal and interpretable activity profile (Zalewska-Piątek, 2023). Crucially, qualification is not a one-time event. As bacterial populations evolve and new genomic insights emerge, phages may require periodic re-evaluation. This reinforces the notion of phage biobanks as dynamic infrastructures rather than static archives. Continuous curation, re-annotation, and contextual updating are integral to maintaining the relevance of the collection over time.
By formalizing the transition from isolation to qualification, phage biobanks establish a common language between microbiology, genomics, and translational application (Resch et al., 2024). In doing so, they create the conditions necessary for downstream integration with predictive tools and decision-support systems, positioning qualified phages not merely as biological entities, but as informed therapeutic assets.
4 Predictive phage biobanks: from catalogs to decision engines
Once phages are qualified and curated within a biobank, their value is no longer defined solely by their biological properties, but by how effectively they can inform therapeutic decisions. In this context, the role of phage biobanks evolves from that of catalogs of biological material to decision-support infrastructures capable of guiding phage selection under time-sensitive conditions. This transition marks a critical inflection point for the scalability of precision phage therapy.
Predictive capacity in phage biobanks does not rely on a single computational approach, but on the integration of multiple layers of information generated during the qualification process. Genomic data, host-range profiles, and contextual metadata together create a structured knowledge base that can be interrogated to infer likely phage–host compatibility (Baláž et al., 2023). Rather than replacing experimental validation, predictive frameworks serve to narrow the solution space, enabling faster and more rational prioritization of candidate phages (Wu et al., 2025). In silico approaches are particularly valuable in addressing the combinatorial complexity imposed by host specificity. As biobanks expand to encompass hundreds or thousands of phages and an equally diverse array of bacterial hosts, exhaustive empirical screening becomes increasingly impractical. Computational inference (drawing on genomic signatures, comparative analyses, and accumulated interaction data) offers a means to triage candidates efficiently while preserving biological interpretability (Nie et al., 2024). An important conceptual development in this context is the notion of standardized phage metadata, which could be described as “phage passports” (Green, 2024). These structured descriptors consolidate essential information, including genomic identity, safety status, functional qualification, and known host associations. By harmonizing how phages are described and queried, phage passports could enable interoperability across biobanks and facilitate the integration of predictive tools without imposing methodological uniformity.
Crucially, the predictive capacity of phage biobanks is fundamentally constrained by methodological heterogeneity across both wet-lab and in silico workflows. Reliable prediction of phage–host interactions, lytic potential, or therapeutic suitability depends on the availability of high-quality, comparable phage and bacterial genomes; however, no harmonized standards currently exist for phage DNA extraction, library preparation, sequencing strategies, genome assembly, or annotation (Mora-Domínguez and Calero-Cáceres, 2025). Variability at any of these stages propagates into downstream analyses, limiting the interpretability and transferability of predictive models (Jansz and Faulkner, 2024). In parallel, computational approaches for host-range inference and functional annotation remain under active development, with a substantial fraction of phage coding sequences still lacking confident functional assignments. Accordingly, prediction should be viewed not as a stand-alone computational solution, but as an emergent property of systematically qualified, coherently annotated, and methodologically standardized biobank datasets. These considerations underscore that the transition from catalogs to truly predictive phage biobanks requires deliberate harmonization of experimental and analytical pipelines, thereby setting the stage for broader translational integration and governance considerations. The functional organization of a predictive phage biobank —integrating targeted recovery, functional feasibility assessment, genomic qualification, and in silico decision support— is summarized in Figure 1.
Figure 1
Conceptual architecture of a predictive phage biobank supporting precision antimicrobial applications.
5 Translational integration across one health
The translational value of phage biobanks extends beyond any single sector, reflecting the ecological reality that antimicrobial resistance circulates across human, animal, agricultural, and environmental interfaces. From a One Health perspective, the relevance of phage biobanks is not defined by sector-specific applications, but by their ability to support precision interventions across interconnected systems (Jo et al., 2023). This integration emerges not as an added conceptual layer, but as a direct consequence of infrastructural design capable of operating across biological and institutional boundaries.
Across domains, the functional requirements for phage deployment are largely shared. Whether applied to multidrug-resistant infections in clinical settings, bacterial diseases in livestock, or pathogen control in agricultural systems, effective phage use depends on rapid access to qualified phages, reliable host matching, and contextual interpretation of activity (Faruk et al., 2025). Differences between sectors primarily concern deployment tempo and regulatory context rather than underlying biological principles: clinical applications often require rapid, case-specific responses, whereas veterinary and agricultural contexts may prioritize preventive or population-level strategies (Strathdee et al., 2023; Marino et al., 2025). A single biobank infrastructure can accommodate these divergent needs by supporting multiple operational modes, provided that qualification standards and data structures remain interoperable.
Importantly, many priority bacterial pathogens traverse sectoral boundaries, including Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Enterococcus spp., frequently carrying shared resistance determinants (Birlutiu and Birlutiu, 2025; Sati et al., 2025). Phage biobanks structured around such taxa can therefore generate cross-sector benefits, enabling reuse of qualified phages and associated knowledge without duplicating discovery efforts. Beyond direct intervention, this integrative capacity also supports surveillance and preparedness by linking phage collections to evolving bacterial landscapes. In this sense, the principal challenge for One Health implementation is not phage applicability, but infrastructural fragmentation. Interoperable phage biobanks offer a shared backbone for discovery, qualification, and deployment, enabling coordinated responses to antimicrobial resistance that reflect the biological continuity of the problem itself.
6 Governance, standardization, and the future of phage biobank infrastructure
The capacity of phage biobanks to function as effective infrastructure depends not only on scientific rigor, but also on governance and standardization frameworks that enable interoperability, scalability, and long-term viability. In the absence of such enabling structures, even well-curated collections risk fragmentation, duplication of effort, and limited translational impact (Bledsoe and Watson, 2025; Mayrhofer, 2025). Governance and standardization should therefore be viewed not as ancillary considerations, but as foundational conditions that allow phage biobanks to evolve from isolated initiatives into coordinated systems supporting precision antimicrobial interventions (Mutalik and Arkin, 2022).
Standardization is central to this transition, particularly with respect to phage qualification, conservation procedures, purification workflows, genomic annotation, and minimal functional metadata (Luong et al., 2020; Turner et al., 2021; Mora-Domínguez and Calero-Cáceres, 2025). Harmonized descriptors enable phages to be meaningfully compared, exchanged, and deployed across institutions without imposing methodological uniformity. Rather than enforcing identical protocols, standardization establishes shared reference points that allow diverse experimental and analytical pipelines to converge into interoperable outputs, forming the basis for predictive tools, regulatory dialogue, and cross-institutional collaboration.
Looking forward, the long-term impact of phage biobanks will depend on their ability to operate as sustained, coordinated infrastructure embedded within public-health and research ecosystems. Interoperable biobank networks, supported by hub-and-spoke governance models, can accommodate local needs while maintaining coherence across clinical, veterinary, and agricultural domains. Recognizing phage biobanks as public-good infrastructure (rather than short-lived research projects) provides a rationale for sustained institutional support and integration with surveillance and diagnostic pipelines. In this sense, phage biobanks form the backbone of future phage therapeutic ecosystems, enabling the field to move beyond proof-of-concept applications toward a scalable and resilient response to antimicrobial resistance.
Statements
Author contributions
PT-P: Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. KM: Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. DP-M: Investigation, Writing – original draft, Writing – review & editing. CF-H: Investigation, Writing – original draft, Writing – review & editing. AA-C: Data curation, Investigation, Methodology, Writing – original draft, Writing – review & editing. JG: Data curation, Methodology, Writing – original draft, Writing – review & editing. KV-L: Investigation, Writing – original draft, Writing – review & editing. MA: Investigation, Writing – original draft, Writing – review & editing. JM-D: Investigation, Writing – original draft, Writing – review & editing. WC-C: Conceptualization, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. This study was supported by the Ecuadorian Corporation for the Development of Research and Academia (CEDIA) (Project UTA code number PEFCIAL15).
Acknowledgments
The authors acknowledge the Vice-Rectory for Research and the Dirección de Investigación y Desarrollo of the Universidad Técnica de Ambato (UTA) for covering the publication fees and for providing institutional support and facilities for the execution of the research activities. The authors also thank Jael Galarza-Mayorga, Gabriela Silva-Arellano, and Justin Santamaría for their excellent technical assistance.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Summary
Keywords
antimicrobial resistance (AMR), bioinformatics, One health, phage biobanks, phage therapy, precision medicine
Citation
Topa-Pila P, Morales KY, Palacios-Mora DP, Flores-Hernández C, Altamirano-Cisneros A, Gavilanes JM, Villacís-López K, Arancibia M, Mora-Domínguez J and Calero-Cáceres W (2026) Phage biobanks as enabling infrastructure for precision phage therapy in the era of antimicrobial resistance. Front. Antibiot. 5:1772871. doi: 10.3389/frabi.2026.1772871
Received
21 December 2025
Revised
30 December 2025
Accepted
05 January 2026
Published
30 January 2026
Corrected
11 February 2026
Volume
5 - 2026
Edited by
Tao Li, Chinese Academy of Agricultural Sciences, China
Reviewed by
Gilbert Verbeken, Queen Astrid Military Hospital, Brussels, Belgium
Updates
Copyright
© 2026 Topa-Pila, Morales, Palacios-Mora, Flores-Hernández, Altamirano-Cisneros, Gavilanes, Villacís-López, Arancibia, Mora-Domínguez and Calero-Cáceres.
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*Correspondence: William Calero-Cáceres, wr.calero@uta.edu.ec
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.