GBD 2021 Antimicrobial Resistance Collaborators Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050. Lancet 404, 1199–1226 (2024).
Dadgostar, P. Antimicrobial resistance: implications and costs. Infect. Drug Resist. 12, 3903–3910 (2019).
Gordillo Altamirano, F. L. & Barr, J. J. Phage therapy in the postantibiotic era. Clin. Microbiol. Rev. 32, e00066–18 (2019).
Gomez-Ochoa, S. A. et al. Efficacy of phage therapy in preclinical models of bacterial infection: a systematic review and meta-analysis. Lancet Microbe 3, e956–e968 (2022).
Uyttebroek, S. et al. Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. Lancet Infect. Dis. 22, e208–e220 (2022).
Marchi, J., Zborowsky, S., Debarbieux, L. & Weitz, J. S. The dynamic interplay of bacteriophage, bacteria and the mammalian host during phage therapy. iScience 26, 106004 (2023).
Vandamme, P. A. et al. Bordetella bronchialis sp. nov., Bordetella flabilis sp. nov. and Bordetella sputigena sp. nov., isolated from human respiratory specimens, and reclassification of Achromobacter sediminum Zhang et al. 2014 as Verticia sediminum gen. nov., comb. nov. Int. J. Syst. Evol. Microbiol. 65, 3674–3682 (2015).
Spilker, T., Darrah, R. & LiPuma, J. J. Complete genome sequences of Bordetella flabilis, Bordetella bronchialis, and “Bordetella pseudohinzii”. Genome Announc. 4, e01132-16 (2016).
Bridel, S. et al. A comprehensive resource for Bordetella genomic epidemiology and biodiversity studies. Nat. Commun. 13, 3807 (2022).
Bonilla, N. et al. Phage on tap-a quick and efficient protocol for the preparation of bacteriophage laboratory stocks. PeerJ 4, e2261 (2016).
Subedi, D. et al. Rational design of a hospital-specific phage cocktail to treat Enterobacter cloacae complex infections. Nat. Microbiol. 10, 2702–2719 (2025).
Khatami, A. et al. Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial. BMJ Open 12, e065401 (2022).
Gembara, K. & Dabrowska, K. Phage-specific antibodies. Curr. Opin. Biotechnol. 68, 186–192 (2021).
Jerne, N. K. & Avegno, P. The development of the phage-inactivating properties of serum during the course of specific immunization of an animal: reversible and irreversible inactivation. J. Immunol. 76, 200–208 (1956).
Hodyra-Stefaniak, K. et al. Natural and induced antibodies against phages in humans: induction kinetics and immunogenicity for structural proteins of PB1-related phages. Phage 1, 91–99 (2020).
Kazmierczak, Z. et al. Immune response to therapeutic staphylococcal bacteriophages in mammals: kinetics of induction, immunogenic structural proteins, natural and induced antibodies. Front. Immunol. 12, 639570 (2021).
Le, H. T. et al. Differences in phage recognition and immunogenicity contribute to divergent human immune responses to Escherichia coli and Klebsiella pneumoniae phages. Eur. J. Immunol. 55, e202451543 (2025).
Lusiak-Szelachowska, M., Miedzybrodzki, R., Fortuna, W., Borysowski, J. & Gorski, A. Anti-phage serum antibody responses and the outcome of phage therapy. Folia Microbiol. 66, 127–131 (2021).
Lusiak-Szelachowska, M. et al. Phage neutralization by sera of patients receiving phage therapy. Viral Immunol. 27, 295–304 (2014).
Dedrick, R. M. et al. Phage therapy of mycobacterium infections: compassionate use of phages in 20 patients with drug-resistant mycobacterial disease. Clin. Infect. Dis. 76, 103–112 (2023).
Lusiak-Szelachowska, M. et al. Antiphage activity of sera during phage therapy in relation to its outcome. Future Microbiol. 12, 109–117 (2017).
Van Belleghem, J. D., Dabrowska, K., Vaneechoutte, M., Barr, J. J. & Bollyky, P. L. Interactions between bacteriophage, bacteria, and the mammalian immune system. Viruses 11, 10 (2018).
Popescu, M., Van Belleghem, J. D., Khosravi, A. & Bollyky, P. L. Bacteriophages and the immune system. Annu. Rev. Virol. 8, 415–435 (2021).
Bichet, M. C., Patwa, R. & Barr, J. J. Protocols for studying bacteriophage interactions with in vitro epithelial cell layers. STAR Protoc. 2, 100697 (2021).
Haddock, N. L., Barkal, L. J. & Bollyky, P. L. Bacteriophage populations mirror those of bacterial pathogens at sites of infection. mSystems 8, e0049723 (2023).
Haddock, N. L. et al. Phage diversity in cell-free DNA identifies bacterial pathogens in human sepsis cases. Nat. Microbiol. 8, 1495–1507 (2023).
Nayfach, S. et al. CheckV assesses the quality and completeness of metagenome-assembled viral genomes. Nat. Biotechnol. 39, 578–585 (2021).
Egido, J. E., Costa, A. R., Aparicio-Maldonado, C., Haas, P. J. & Brouns, S. J. J. Mechanisms and clinical importance of bacteriophage resistance. FEMS Microbiol. Rev. 46, fuab048 (2022).
Lebeaux, D. et al. A case of phage therapy against pandrug-resistant Achromobacter xylosoxidans in a 12-year-old lung-transplanted cystic fibrosis patient. Viruses 13, 60 (2021).
Blasco, L. et al. Case report: analysis of phage therapy failure in a patient with a Pseudomonas aeruginosa prosthetic vascular graft infection. Front. Med. 10, 1199657 (2023).
Jault, P. et al. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial. Lancet Infect. Dis. 19, 35–45 (2019).
Schooley, R. T. et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob. Agents Chemother. 61, e00954–17 (2017).
Gordillo Altamirano, F. L. et al. Phage-antibiotic combination is a superior treatment against Acinetobacter baumannii in a preclinical study. EBioMedicine 80, 104045 (2022).
Zhvania, P., Hoyle, N. S., Nadareishvili, L., Nizharadze, D. & Kutateladze, M. Phage therapy in a 16-year-old boy with Netherton syndrome. Front. Med. 4, 94 (2017).
Bertozzi Silva, J., Storms, Z. & Sauvageau, D. Host receptors for bacteriophage adsorption. FEMS Microbiol. Lett. 363, fnw002 (2016).
Happonen, L. J., Pajunen, M. I., Jun, J. W. & Skurnik, M. BtuB-dependent infection of the T5-like Yersinia phage varphiR2-01. Viruses 13, 2171 (2021).
Hong, J. et al. Identification of host receptor and receptor-binding module of a newly sequenced T5-like phage EPS7. FEMS Microbiol. Lett. 289, 202–209 (2008).
Golomidova, A. K. et al. Branched lateral tail fiber organization in T5-like bacteriophages DT57C and DT571/2 is revealed by genetic and functional analysis. Viruses 8, 26 (2016).
Gordillo Altamirano, F. L. & Barr, J. J. Unlocking the next generation of phage therapy: the key is in the receptors. Curr. Opin. Biotechnol. 68, 115–123 (2021).
Gillis, A. & Mahillon, J. An improved method for rapid generation and screening of Bacillus thuringiensis phage-resistant mutants. J. Microbiol. Methods 106, 101–103 (2014).
Andersson, D. I., Nicoloff, H. & Hjort, K. Mechanisms and clinical relevance of bacterial heteroresistance. Nat. Rev. Microbiol. 17, 479–496 (2019).
Meng, J., Young, G. & Chen, J. The Rcs system in Enterobacteriaceae: envelope stress responses and virulence regulation. Front. Microbiol. 12, 627104 (2021).
Wall, E., Majdalani, N. & Gottesman, S. The complex Rcs regulatory cascade. Annu. Rev. Microbiol. 72, 111–139 (2018).
Chaudhry, W. et al. Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria. FEMS Microbiol. Ecol. 96, fiaa162 (2020).
Mutalik, V. K. et al. High-throughput mapping of the phage resistance landscape in E. coli. PLoS Biol. 18, e3000877 (2020).
Smith, L. M. et al. The Rcs stress response inversely controls surface and CRISPR–Cas adaptive immunity to discriminate plasmids and phages. Nat. Microbiol. 6, 162–172 (2021).
Burmeister, A. R., Tewatia, H. & Skinner, C. A tradeoff between bacteriophage resistance and bacterial motility is mediated by the Rcs phosphorelay in Escherichia coli. Microbiology 170, 001491 (2024).
Kortright, K. E., Chan, B. K. & Turner, P. E. High-throughput discovery of phage receptors using transposon insertion sequencing of bacteria. Proc. Natl Acad. Sci. USA 117, 18670–18679 (2020).
Acton, L. et al. Collateral sensitivity increases the efficacy of a rationally designed bacteriophage combination to control Salmonella enterica. J. Virol. 98, e0147623 (2024).
Bai, J., Raustad, N., Denoncourt, J., van Opijnen, T. & Geisinger, E. Genome-wide phage susceptibility analysis in Acinetobacter baumannii reveals capsule modulation strategies that determine phage infectivity. PLoS Pathog. 19, e1010928 (2023).
Nyenhuis, D. A., Nilaweera, T. D. & Cafiso, D. S. Native cell environment constrains loop structure in the Escherichia coli cobalamin transporter BtuB. Biophys. J. 119, 1550–1557 (2020).
Shearer, J., Jefferies, D. & Khalid, S. Outer membrane proteins OmpA, FhuA, OmpF, EstA, BtuB, and OmpX have unique lipopolysaccharide fingerprints. J. Chem. Theory Comput. 15, 2608–2619 (2019).
Halperin, S. A., Ferrieri, P., Gray, E. D., Kaplan, E. L. & Wannamaker, L. W. Antibody response to bacteriophage hyaluronidase in acute glomerulonephritis after group A streptococcal infection. J. Infect. Dis. 155, 253–261 (1987).
Fluckiger, A. et al. Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage. Science 369, 936–942 (2020).
Berkson, J. D. et al. Phage-specific immunity impairs efficacy of bacteriophage targeting vancomycin resistant Enterococcus in a murine model. Nat. Commun. 15, 2993 (2024).
Zborowsky, S. et al. Macrophage-induced reduction of bacteriophage density limits the efficacy of in vivo pulmonary phage therapy. Nat. Commun. 16, 5725 (2025).
Roach, D. R. et al. Synergy between the host immune system and bacteriophage is essential for successful phage therapy against an acute respiratory pathogen. Cell Host Microbe 22, 38–47 (2017).
Dewachter, L., Fauvart, M. & Michiels, J. Bacterial heterogeneity and antibiotic survival: understanding and combatting persistence and heteroresistance. Mol. Cell 76, 255–267 (2019).
Klein, S. et al. Comparative genomic reveals clonal heterogeneity in persistent Staphylococcus aureus infection. Front. Cell. Infect. Microbiol. 12, 817841 (2022).
Bartell, J. A. et al. Evolutionary highways to persistent bacterial infection. Nat. Commun. 10, 629 (2019).
Stachurska, X., Roszak, M., Jablonska, J., Mizielinska, M. & Nawrotek, P. Double-layer agar (DLA) modifications for the first step of the phage-antibiotic synergy (PAS) identification. Antibiotics 10, 1306 (2021).
Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114–2120 (2014).
Wick, R. R., Judd, L. M., Gorrie, C. L. & Holt, K. E. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol. 13, e1005595 (2017).
Seemann, T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069 (2014).
Aziz, R. K. et al. The RAST server: rapid annotations using subsystems technology. BMC Genomics 9, 75 (2008).
Terzian, P. et al. PHROG: families of prokaryotic virus proteins clustered using remote homology. NAR Genom. Bioinform. 3, lqab067 (2021).
Shen, W., Le, S., Li, Y. & Hu, F. SeqKit: a cross-platform and ultrafast toolkit for FASTA/Q file manipulation. PLoS ONE 11, e0163962 (2016).
Walker, B. J. et al. Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE 9, e112963 (2014).
Feldgarden, M. et al. AMRFinderPlus and the Reference Gene Catalog facilitate examination of the genomic links among antimicrobial resistance, stress response, and virulence. Sci. Rep. 11, 12728 (2021).
Bin Jang, H. et al. Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks. Nat. Biotechnol. 37, 632–639 (2019).
Nayfach, S. et al. Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nat. Microbiol. 6, 960–970 (2021).
Cook, R. et al. INfrastructure for a PHAge REference Database: identification of large-scale biases in the current collection of cultured phage genomes. Phage 2, 214–223 (2021).
Turner, D. et al. Abolishment of morphology-based taxa and change to binomial species names: 2022 taxonomy update of the ICTV bacterial viruses subcommittee. Arch. Virol. 168, 74 (2023).
Jespersen, M. C., Peters, B., Nielsen, M. & Marcatili, P. BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes. Nucleic Acids Res. 45, W24–W29 (2017).
Wick, R. R. et al. Trycycler: consensus long-read assemblies for bacterial genomes. Genome Biol. 22, 266 (2021).
Wick, R. R. & Holt, K. E. Polypolish: Short-read polishing of long-read bacterial genome assemblies. PLoS Comput. Biol. 18, e1009802 (2022).
Schwengers, O. et al. Bakta: rapid and standardized annotation of bacterial genomes via alignment-free sequence identification. Microb. Genom. 7, 000685 (2021).
Hawkey, J. et al. ISMapper: identifying transposase insertion sites in bacterial genomes from short read sequence data. BMC Genomics 16, 667 (2015).
Tonkin-Hill, G. et al. Producing polished prokaryotic pangenomes with the Panaroo pipeline. Genome Biol. 21, 180 (2020).
Stamatakis, A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30, 1312–1313 (2014).
Paradis, E. & Schliep, K. ape 5.0: an environment for modern phylogenetics and evolutionary analyses in R. Bioinformatics 35, 526–528 (2019).
Yu, G. Using ggtree to visualize data on tree-like structures. Curr. Protoc. Bioinform. 69, e96 (2020).