Yuan Y, Gao M. Jumbo bacteriophages: an overview. Front Microbiol. 2017;8:403.
Al-Shayeb B, Sachdeva R, Chen LX, Ward F, Munk P, Devoto A, et al. Clades of huge phages from across earth’s ecosystems. Nature. 2020;578:425–31.
Chaikeeratisak V, Nguyen K, Khanna K, Brilot AF, Erb ML, Coker JK, et al. Assembly of a nucleus-like structure during viral replication in bacteria. Science. 2017;355:194–7.
Laughlin TG, Deep A, Prichard AM, Seitz C, Gu Y, Enustun E, et al. Architecture and self-assembly of the jumbo bacteriophage nuclear shell. Nature. 2022;608:429–35.
Mendoza SD, Nieweglowska ES, Govindarajan S, Leon LM, Berry JD, Tiwari A, et al. A bacteriophage nucleus-like compartment shields DNA from crispr nucleases. Nature. 2020;577:244–8.
Nguyen KT, Sugie J, Khanna K, Egan ME, Birkholz EA, Lee J, et al. Selective transport of fluorescent proteins into the phage nucleus. PLoS One. 2021;16:e0251429.
Chaikeeratisak V, Khanna K, Nguyen KT, Egan ME, Enustun E, Armbruster E, et al. Subcellular organization of viral particles during maturation of nucleus-forming jumbo phage. Sci Adv. 2022;8:eabj9670.
Krylov V, Bourkaltseva M, Pleteneva E, Shaburova O, Krylov S, Karaulov A, et al. Phage phikz-the first of giants. Viruses. 2021. https://doi.org/10.3390/v13020149
Wu W, Thomas JA, Cheng N, Black LW, Steven AC. Bubblegrams reveal the inner body of bacteriophage phikz. Science. 2012;335:182.
Thomas JA, Weintraub ST, Wu W, Winkler DC, Cheng N, Steven AC, et al. Extensive proteolysis of head and inner body proteins by a morphogenetic protease in the giant pseudomonas aeruginosa phage phikz. Mol Microbiol. 2012;84:324–39.
Mozumdar D, Fossati A, Stevenson E, Guan J, Nieweglowska E, Rao S, et al. Characterization of a lipid-based jumbo phage compartment as a hub for early phage infection. Cell Host Microbe. 2024;32(1050–58):e7.
Gerovac M, Chihara K, Wicke L, Bottcher B, Lavigne R, Vogel J. Phage proteins target and co-opt host ribosomes immediately upon infection. Nat Microbiol. 2024;9:787–800.
Morgan CJ, Enustun E, Armbruster EG, Birkholz EA, Prichard A, Forman T, et al. An essential and highly selective protein import pathway encoded by nucleus-forming phage. Proc Natl Acad Sci U S A. 2024;121:e2321190121.
Enustun E, Armbruster EG, Lee J, Zhang S, Yee BA, Malukhina K, et al. A phage nucleus-associated rna-binding protein is required for jumbo phage infection. Nucleic Acids Res. 2024;52:4440–55.
Chaikeeratisak V, Khanna K, Nguyen KT, Sugie J, Egan ME, Erb ML, et al. Viral capsid trafficking along treadmilling tubulin filaments in bacteria. Cell. 2019;177(1771–80):e12.
Malone LM, Warring SL, Jackson SA, Warnecke C, Gardner PP, Gumy LF, et al. A jumbo phage that forms a nucleus-like structure evades crispr-cas DNA targeting but is vulnerable to type iii rna-based immunity. Nat Microbiol. 2020;5:48–55.
Birkholz EA, Laughlin TG, Armbruster E, Suslov S, Lee J, Wittmann J, et al. A cytoskeletal vortex drives phage nucleus rotation during jumbo phage replication in e. Coli. Cell Rep. 2022;40:111179.
Prichard A, Lee J, Laughlin TG, Lee A, Thomas KP, Sy AE, et al. Identifying the core genome of the nucleus-forming bacteriophage family and characterization of Erwinia phage ray. Cell Rep. 2023;42:112432.
Wang W, Ren J, Tang K, Dart E, Ignacio-Espinoza JC, Fuhrman JA, et al. A network-based integrated framework for predicting virus-prokaryote interactions. NAR Genom Bioinform. 2020;2:lqaa044.
Li Y, Guan J, Hareendranath S, Crawford E, Agard DA, Makarova KS et al. A family of novel immune systems targets early infection of nucleus-forming jumbo phages. bioRxiv. 2022:2022.09.17.508391. https://doi.org/10.1101/2022.09.17.508391.
Wakui D, Nagashima G, Otsuka Y, Takada T, Ueda T, Tanaka Y, et al. A case of meningitis due to neisseria subflava after ventriculostomy. J Infect Chemother. 2012;18:115–8.
Lee MR, Sheng WH, Hung CC, Yu CJ, Lee LN, Hsueh PR. Mycobacterium abscessus complex infections in humans. Emerg Infect Dis. 2015;21:1638–46.
Shkoporov AN, Hill C. Bacteriophages of the human gut: The “known unknown” of the microbiome. Cell Host Microbe. 2019;25:195–209.
Prichard A, Sy A, Meyer J, Villa E, Pogliano J. Erwinia phage asesino is a nucleus-forming phage that lacks phuz. Sci Rep. 2025;15:1692.
Chaikeeratisak V, Nguyen K, Egan ME, Erb ML, Vavilina A, Pogliano J. The phage nucleus and tubulin spindle are conserved among large pseudomonas phages. Cell Rep. 2017;20:1563–71.
Mann S, Chen YP. Bacterial genomic g+c composition-eliciting environmental adaptation. Genomics. 2010;95:7–15.
Kakasis A, Panitsa G. Bacteriophage therapy as an alternative treatment for human infections. A comprehensive review. Int J Antimicrob Agents. 2019;53:16–21.
Devoto AE, Santini JM, Olm MR, Anantharaman K, Munk P, Tung J, et al. Megaphages infect Prevotella and variants are widespread in gut microbiomes. Nat Microbiol. 2019;4:693–700.
Fierst JL, Willis JH, Thomas CG, Wang W, Reynolds RM, Ahearne TE, et al. Reproductive mode and the evolution of genome size and structure in caenorhabditis nematodes. PLoS Genet. 2015;11:e1005323.
Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974;78:737–56.
Murphy J, Klumpp J, Mahony J, O’Connell-Motherway M, Nauta A, van Sinderen D. Methyltransferases acquired by lactococcal 936-type phage provide protection against restriction endonuclease activity. BMC Genomics. 2014;15:831.
Bobonis J, Mitosch K, Mateus A, Karcher N, Kritikos G, Selkrig J, et al. Bacterial retrons encode phage-defending tripartite toxin-antitoxin systems. Nature. 2022;609:144–50.
Leavitt A, Yirmiya E, Amitai G, Lu A, Garb J, Herbst E, et al. Viruses inhibit Tir gcadpr signalling to overcome bacterial defence. Nature. 2022;611:326–31.
Popova AV, Shneider MM, Arbatsky NP, Kasimova AA, Senchenkova SN, Shashkov AS, et al. Specific interaction of novel friunavirus phages encoding tailspike depolymerases with corresponding Acinetobacter baumannii capsular types. J Virol. 2021. https://doi.org/10.1128/JVI.01714-20.
Yang B, Zheng J, Yin Y. Acafinder: genome mining for anti-crispr-associated genes. mSystems. 2022;7:e0081722.
Hobbs SJ, Wein T, Lu A, Morehouse BR, Schnabel J, Leavitt A, et al. Phage anti-cbass and anti-pycsar nucleases subvert bacterial immunity. Nature. 2022;605:522–6.
Azam AH, Chihara K, Kondo K, Nakamura T, Ojima S, Tamura A et al. Viruses encode trna and anti-retron to evade bacterial immunity. bioRxiv. 2023:2023.03.15.532788. https://doi.org/10.1101/2023.03.15.532788.
Murphy KC, Lewis LJ. Properties of Escherichia coli expressing bacteriophage p22 abc (anti-recbcd) proteins, including inhibition of chi activity. J Bacteriol. 1993;175(6):1756–66.
Camargo AP, Nayfach S, Chen IA, Palaniappan K, Ratner A, Chu K, et al. Img/vr v4: An expanded database of uncultivated virus genomes within a framework of extensive functional, taxonomic, and ecological metadata. Nucleic Acids Res. 2023;51:D733–43.
Weinheimer AR, Aylward FO. Infection strategy and biogeography distinguish cosmopolitan groups of marine jumbo bacteriophages. ISME J. 2022;16(6):1657–67.
Nayfach S, Paez-Espino D, Call L, Low SJ, Sberro H, Ivanova NN, et al. Metagenomic compendium of 189,680 DNA viruses from the human gut microbiome. Nat Microbiol. 2021;6:960–70.
Camarillo-Guerrero LF, Almeida A, Rangel-Pineros G, Finn RD, Lawley TD. Massive expansion of human gut bacteriophage diversity. Cell. 2021;184(1098–109):e9.
Benler S, Yutin N, Antipov D, Rayko M, Shmakov S, Gussow AB, et al. Thousands of previously unknown phages discovered in whole-community human gut metagenomes. Microbiome. 2021;9:78.
Terzian P, Olo Ndela E, Galiez C, Lossouarn J, Perez Bucio RE, Mom R, et al. Phrog: Families of prokaryotic virus proteins clustered using remote homology. NAR Genom Bioinform. 2021;3:lqab067.
Grazziotin AL, Koonin EV, Kristensen DM. Prokaryotic virus orthologous groups (pvogs): a resource for comparative genomics and protein family annotation. Nucleic Acids Res. 2017;45:D491-8.
Huerta-Cepas J, Szklarczyk D, Forslund K, Cook H, Heller D, Walter MC, et al. Eggnog 4.5: A hierarchical orthology framework with improved functional annotations for eukaryotic, prokaryotic and viral sequences. Nucleic Acids Res. 2016;44:D286-93.
El-Gebali S, Mistry J, Bateman A, Eddy SR, Luciani A, Potter SC, et al. The pfam protein families database in 2019. Nucleic Acids Res. 2019;47:D427–32.
Aramaki T, Blanc-Mathieu R, Endo H, Ohkubo K, Kanehisa M, Goto S, et al. Kofamkoala: kegg ortholog assignment based on profile hmm and adaptive score threshold. Bioinformatics. 2020;36:2251–2.
Katoh K, Standley DM. Mafft multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol. 2013;30:772–80.
Eddy SR. Accelerated profile hmm searches. PLoS Comput Biol. 2011;7:e1002195.
Hyatt D, Chen GL, Locascio PF, Land ML, Larimer FW, Hauser LJ. Prodigal: prokaryotic gene recognition and translation initiation site identification. BMC Bioinformatics. 2010;11:119.
Shen W, Le S, Li Y, Hu F. Seqkit: a cross-platform and ultrafast toolkit for fasta/q file manipulation. PLoS One. 2016;11:e0163962.
Baek M, DiMaio F, Anishchenko I, Dauparas J, Ovchinnikov S, Lee GR, et al. Accurate prediction of protein structures and interactions using a three-track neural network. Science. 2021;373:871–6.
van Kempen M, Kim SS, Tumescheit C, Mirdita M, Lee J, Gilchrist CLM, et al. Fast and accurate protein structure search with foldseek. Nat Biotechnol. 2024;42(2):243–6.
Olm MR, Brown CT, Brooks B, Banfield JF. Drep: a tool for fast and accurate genomic comparisons that enables improved genome recovery from metagenomes through de-replication. ISME J. 2017;11:2864–8.
Nayfach S, Camargo AP, Schulz F, Eloe-Fadrosh E, Roux S, Kyrpides NC. Checkv assesses the quality and completeness of metagenome-assembled viral genomes. Nat Biotechnol. 2021;39:578–85.
Kieft K, Zhou Z, Anantharaman K. Vibrant: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences. Microbiome. 2020;8:90.
Tesson F, Huiting E, Wei L, Ren J, Johnson M, Planel R, et al. Exploring the diversity of anti-defense systems across prokaryotes, phages and mobile genetic elements. Nucleic Acids Res. 2025. https://doi.org/10.1093/nar/gkae1171.
Bin Jang H, Bolduc B, Zablocki O, Kuhn JH, Roux S, Adriaenssens EM, et al. Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks. Nat Biotechnol. 2019;37:632–9.
Couvin D, Bernheim A, Toffano-Nioche C, Touchon M, Michalik J, Neron B, et al. Crisprcasfinder, an update of crisrfinder, includes a portable version, enhanced performance and integrates search for cas proteins. Nucleic Acids Res. 2018;46:W246–51.
Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K, et al. Blast+: architecture and applications. BMC Bioinformatics. 2009;10:421.
Luo XQ, Wang P, Li JL, Ahmad M, Duan L, Yin LZ, et al. Viral community-wide auxiliary metabolic genes differ by lifestyles, habitats, and hosts. Microbiome. 2022;10:190.
Howell AA, Versoza CJ, Pfeifer SP. Computational host range prediction-the good, the bad, and the ugly. Virus Evol. 2024;10:vead083.
Shang J, Sun Y. Cherry: a computational method for accurate prediction of virus-prokaryotic interactions using a graph encoder-decoder model. Brief Bioinform. 2022. https://doi.org/10.1093/bib/bbac182.
Amgarten D, Iha BKV, Piroupo CM, da Silva AM, Setubal JC. Vhulk, a new tool for bacteriophage host prediction based on annotated genomic features and neural networks. PHAGE. 2022;3:204–12.
Capella-Gutierrez S, Silla-Martinez JM, Gabaldon T. Trimal: a tool for automated alignment trimming in large-scale phylogenetic analyses. Bioinformatics. 2009;25:1972–3.
Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD, von Haeseler A, et al. Iq-tree 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol. 2020;37:1530–4.
Fu L, Niu B, Zhu Z, Wu S, Li W. Cd-hit: accelerated for clustering the next-generation sequencing data. Bioinformatics. 2012;28(23):3150–2.
Price MN, Dehal PS, Arkin AP. Fasttree 2–approximately maximum-likelihood trees for large alignments. PLoS One. 2010;5:e9490.
Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30:2068–9.
Ding W, Baumdicker F, Neher RA. Panx: pan-genome analysis and exploration. Nucleic Acids Res. 2018;46:e5.
Chan PP, Lowe TM. Trnascan-se: Searching for trna genes in genomic sequences. Methods Mol Biol. 2019;1962:1–14.
Sullivan MJ, Petty NK, Beatson SA. Easyfig: a genome comparison visualizer. Bioinformatics. 2011;27:1009–10.
Lu J, Salzberg SL. Skewit: the skew index test for large-scale GC skew analysis of bacterial genomes. PLoS Comput Biol. 2020;16:e1008439.
Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9:357–9.
Pasolli E, Asnicar F, Manara S, Zolfo M, Karcher N, Armanini F, et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell. 2019;176(649–62):e20.
Morais S, Winkler S, Zorea A, Levin L, Nagies FSP, Kapust N, et al. Cryptic diversity of cellulose-degrading gut bacteria in industrialized humans. Science. 2024;383:eadj9223.
Li R, Wang Y, Hu H, Tan Y, Ma Y. Metagenomic analysis reveals unexplored diversity of archaeal virome in the human gut. Nat Commun. 2022;13:7978.
Li D, Liu CM, Luo R, Sadakane K, Lam TW. Megahit: an ultra-fast single-node solution for large and complex metagenomics assembly via succinct de bruijn graph. Bioinformatics. 2015;31:1674–6.
Kolmogorov M, Raney B, Paten B, Pham S. Ragout-a reference-assisted assembly tool for bacterial genomes. Bioinformatics. 2014;30:i302-9.
Chen T, Liu YX, Huang L. Imagegp: an easy-to-use data visualization web server for scientific researchers. Imeta. 2022;1:e5.
Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2011;27:431–2.
Letunic I, Bork P. Interactive tree of life (itol) v3: an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res. 2016;44:W242–5.