Open research questions in Bacteriophages and microbial interactions
1,049 gap statements mined from Bacteriophages and microbial interactions papers in our 7.9M-paper local library, which holds 3,503 papers on the topic — drawn mostly from each paper's own stated research gap, future-work, challenge and limitation notes, and its abstract. The ones listed below are a selection still marked open; each names the study that raised it, with a DOI link where the paper has one.
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What the literature leaves open
Sequencing errors need to be filtered out to provide certainty on the amount of genetic diversity present. High read depth is required for microdiversity analysis. Disagreement between lifestyle prediction methods can lead to discarding of vOTUs.
Lack of pharmacokinetic data for mycobacteriophages. Incomplete understanding of tissue distribution for mycobacteriophages. Limited understanding of the determinants of phage disposition.
Pharmacokinetics and Physiologically Based Pharmacokinetic Modeling of Mycobacteriophages: Insights into Pulmonary Distribution and Clearance · 2026 · DOIThe lack of effective treatment options for CREC infections. The need for novel therapeutic approaches against multidrug-resistant bacteria.
A novel phage encoding host defense modulators demonstrates in-vivo therapeutic efficacy against carbapenem-resistant E. coli ST1432 · 2026 · DOIThe lack of effective methods to reduce antibiotic, metal, and biocide resistance genes and virulence factors in duck litter. The need to develop sustainable and environmentally friendly methods for managing duck litter. The limited understanding of the effects of compound microbial intelligent membrane fermentation on the bacterial community and resistance genes in duck litter.
Compound microbial intelligent membrane fermentation reshapes the bacterial community and reduces antibiotic, metal, and biocide resistance genes and virulence factors in duck litter · 2026 · DOIThe paper identifies technical challenges in the analysis of phage genomes and proteins, including the need for accurate prediction of gene function and protein structure. It also highlights the challenge of understanding the evolutionary history of phages, including the identification of genetic exchange events and the maintenance of a common genomic architecture.
It also highlights the need for further study of the genetic characteristics and relationships of Pseudomonas phages.
The study does not explicitly state the research gap, but it can be inferred as the lack of understanding of the general characterization of Acinetobacter baumannii and Klebsiella pneumoniae isolates. The study aims to fill this gap by performing general characterization of A. baumannii and K. pneumoniae isolates obtained from intensive care unit patients.
Acinetobacter baumannii and Klebsiella pneumoniae Isolates Obtained from Intensive Care Unit Patients in 2024: General Characterization, Prophages, Depolymerases and Esterases of Phage Origin · 2025 · DOIThe lack of understanding of the strain-level diversity and biotechnological potential of B. animalis subsp. lactis. The need for a comprehensive comparative genomic analysis of this species.
Comparative Genomics of Bifidobacterium animalis subsp. lactis Reveals Strain-Level Hyperdiversity, Carbohydrate Metabolism Adaptations, and CRISPR-Mediated Phage Immunity · 2025 · DOIOne challenge is the possibility of overstimulation of the immune system by phage capsids, tails, and tail fibers. Another challenge is the development of resistance to phage attacks by bacteria. A third challenge is the need for more research on the use of genomically engineered phages in antibacterial applications.
There is a need for the development of genetically stable strains with strong phage resistance. The current state of research on phage resistance mechanisms is not comprehensive. There is a lack of understanding of the complex interactions between phages and bacteria.
The need for further research to address the limitations of phage-based therapies and to fully realize their potential in cancer treatment.
The need to improve the effectiveness of mRNA vaccines against bacterial infections. The challenge of overcoming the increasing resistance of bacteria to existing antibacterial drugs.
The lack of new-generation antibacterial drugs. The increasing resistance of major species of pathogenic bacteria to existing antibacterial drugs. The need for alternative approaches to prevention and treatment of bacterial infections.
The paper identifies the need for standardized approaches in metagenomic sequencing for infectious disease diagnosis. It highlights the limitations of metagenomic sequencing, including low sensitivity due to high background from the host or microbiome.
Enhancing Clinical Utility: Utilization of International Standards and Guidelines for Metagenomic Sequencing in Infectious Disease Diagnosis · 2024 · DOIThe drivers of microdiversity remain poorly understood, particularly in relation to phage lifestyle. The influence of temperate phages integrating themselves into the host genome on microdiversity is unknown.
While existing benchmark studies have focused on viral detection tools using highly-abundant virus-enriched, their performance in low-abundance metagenomic environments remains unexplored.
Benchmarking and integration of viral prediction tools to uncover viral dark matter across divergent low abundance metagenomes · 2026 · DOIDuring the first wave of the seventh cholera pandemic, the Kappa prophage was commonly found in clinical isolates and was later shown to confer a competitive fitness advantage in the environment and to accelerate evolution by stimulating horizontal gene transfer; however, its role in virulence remains unknown.
Kappa Prophage Impacts Vibrio cholerae Fitness and is Restricted by BREX Phage Defense System · 2026 · DOIGiant viruses of the phylum Nucleocytoviricota have expanded the boundaries of virology, yet the mechanisms underlying the gigantism of their genomes remain poorly understood.
However, efficient methods for purifying single-stranded DNA (ssDNA) from filamentous phages are scarce and rely mainly on repurposed commercial kits developed for dsDNA.
Pharmacokinetic data remain especially limited. Current IV and nebulized doses are largely empirical. Statistical analysis was not possible for some comparisons due to reduced sample size.
Pharmacokinetics and Physiologically Based Pharmacokinetic Modeling of Mycobacteriophages: Insights into Pulmonary Distribution and Clearance · 2026 · DOIFurther studies are needed to evaluate the efficacy of Baskent_Phicoli_1 against other strains of CREC, - Research is needed to explore the potential of phage therapy in combination with other treatments, - Studies should investigate the safety and efficacy of phage therapy…
A novel phage encoding host defense modulators demonstrates in-vivo therapeutic efficacy against carbapenem-resistant E. coli ST1432 · 2026 · DOIFurther study of the prophage regions and their relationship to phage diversity, - Investigation of the role of prophages in the evolution of A. baumannii and K.
Acinetobacter baumannii and Klebsiella pneumoniae Isolates Obtained from Intensive Care Unit Patients in 2024: General Characterization, Prophages, Depolymerases and Esterases of Phage Origin · 2025 · DOIIn-depth and well-designed clinical trials are required to assess the efficacy of phage therapy and phage-antibiotic therapy, - Further research on the genetic engineering of phages for antibacterial…
Further investigation of phage therapy through genome engineering, - Combining phage therapy with antibiotics to address the issue of bacterial resistance, - Establishing phage therapy as a standard medical…
Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections · 2024 · DOIReticuloendothelial system clearance, - Diffusion inefficiency, - Limited research on certain cancer types such as lymphoma, cervical cancer…
Most-cited papers in Bacteriophages and microbial interactions
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 · Nature · 1970 · 181,945 citations
- CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes · Science · 2007 · 5,677 citations
- Filamentous Fusion Phage: Novel Expression Vectors That Display Cloned Antigens on the Virion Surface · Science · 1985 · 3,359 citations
- CheckV assesses the quality and completeness of metagenome-assembled viral genomes · Nature Biotechnology · 2020 · 1,789 citations
- VFDB 2022: a general classification scheme for bacterial virulence factors · Nucleic Acids Research · 2021 · 1,781 citations
- VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses · Microbiome · 2021 · 1,314 citations
- VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences · Microbiome · 2020 · 1,193 citations
- VIRIDIC—A Novel Tool to Calculate the Intergenomic Similarities of Prokaryote-Infecting Viruses · Viruses · 2020 · 754 citations
- Diverse enzymatic activities mediate antiviral immunity in prokaryotes · Science · 2020 · 714 citations
- Identifying viruses from metagenomic data using deep learning · Quantitative Biology · 2020 · 686 citations
Most recent work
- The Role of Genomics in Advancing and Standardising Bacteriophage Therapy · Antibiotics · 2026
- Phage Therapy at the Crossroads Between Clinical Promise and Regulatory Challenge · Pharmaceuticals · 2026
- Towards accurate artificial intelligence models for strain-level phage–host prediction · Briefings in Bioinformatics · 2026
- Engineering bacteriophages for gut health: precision antimicrobials and beyond · Journal of Nanobiotechnology · 2026
- Bacteriophage Therapy: Overcoming Antimicrobial Resistance Through Advanced Delivery Methods · Molecules · 2026
- Safety, recovery, and pharmacodynamics of CRISPR–Cas therapeutic SNIPR001: a phase 1, randomised, double-blind, first-in-human, dose-escalation study · The Lancet Microbe · 2026
- Engineered living glues secrete therapeutic proteins for treatment of inflammatory bowel disease · Nature Biotechnology · 2026
- Immune Responses to Phage Therapy in Humans: A Review · The Journal of Infectious Diseases · 2026
- A phage protein screen identifies triggers of the bacterial innate immune system · Nature Microbiology · 2026
- Broth Optical Density-Based Assessment for Phage Therapy: Turbidity Reduction, Antibacterial Virulence, and Time-Kill · Viruses · 2026
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