Buchan, A., LeCleir, G. R., Gulvik, C. A. & Gonzalez, J. M. Master recyclers: features and functions of bacteria associated with phytoplankton blooms. Nat. Rev. Microbiol. 12, 686–698 (2014).
Brinkmann, S., Spohn, M. S. & Schaberle, T. F. Bioactive natural products from Bacteroidetes. Nat. Prod. Rep. 39, 1045–1065 (2022).
Desai, M. S. & Brune, A. Bacteroidales ectosymbionts of gut flagellates shape the nitrogen-fixing community in dry-wood termites. ISME J. 6, 1302–1313 (2012).
Sabree, Z. L., Kambhampati, S. & Moran, N. A. Nitrogen recycling and nutritional provisioning by Blattabacterium, the cockroach endosymbiont. Proc. Natl Acad. Sci. USA 106, 19521–19526 (2009).
Abrahamsen, H. L. et al. Distant relatives of a eukaryotic cell-specific toxin family evolved a complement-like mechanism to kill bacteria. Nat. Commun. 15, 5028 (2024).
Coyne, M. J. et al. A family of anti-Bacteroidales peptide toxins wide-spread in the human gut microbiota. Nat. Commun. 10, 3460 (2019).
Jiang, K. et al. Bacteroides fragilis ubiquitin homologue drives intraspecies bacterial competition in the gut microbiome. Nat. Microbiol. 9, 70–84 (2024).
Hecht, A. L., Casterline, B. W., Choi, V. M. & Bubeck Wardenburg, J. A two-component system regulates Bacteroides fragilis toxin to maintain intestinal homeostasis and prevent lethal disease. Cell Host Microbe 22, 443–448 (2017).
Li, Y. et al. Identification of trypsin-degrading commensals in the large intestine. Nature 609, 582–589 (2022).
Papenfort, K. & Bassler, B. L. Quorum sensing signal-response systems in Gram-negative bacteria. Nat. Rev. Microbiol. 14, 576–588 (2016).
Cao, Y., Forstner, K. U., Vogel, J. & Smith, C. J. cis-encoded small RNAs, a conserved mechanism for repression of polysaccharide utilization in Bacteroides. J. Bacteriol. 198, 2410–2418 (2016).
Adams, A. N. D. et al. A novel family of RNA-binding proteins regulate polysaccharide metabolism in Bacteroides thetaiotaomicron. J. Bacteriol. 203, e0021721 (2021).
Davidson, B. S. & Schumacher, R. W. Isolation and synthesis of caprolactins A and B, new caprolactams from a marine bacterium. Tetrahedron 49, 6569–6574 (1993).
Bayley, D. P., Rocha, E. R. & Smith, C. J. Analysis of cepA and other Bacteroides fragilis genes reveals a unique promoter structure. FEMS Microbiol. Lett. 193, 149–154 (2000).
Elmassry, M. M. et al. A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules. Cell Host Microbe 33, 218–234.e12 (2025).
Ma, X., Jiang, K., Zhou, C., Xue, Y. & Ma, Y. Identification and characterization of a novel GNAT superfamily Nα-acetyltransferase from Salinicoccus halodurans H3B36. Microb. Biotechnol. 15, 1652–1665 (2022).
Duda, D. M., Walden, H., Sfondouris, J. & Schulman, B. A. Structural analysis of Escherichia coli ThiF. J. Mol. Biol. 349, 774–786 (2005).
Lake, M. W., Wuebbens, M. M., Rajagopalan, K. V. & Schindelin, H. Mechanism of ubiquitin activation revealed by the structure of a bacterial MoeB-MoaD complex. Nature 414, 325–329 (2001).
Schulman, B. A. & Harper, J. W. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways. Nat. Rev. Mol. Cell Biol. 10, 319–331 (2009).
Walden, H. et al. The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1. Mol. Cell 12, 1427–1437 (2003).
Lois, L. M. & Lima, C. D. Structures of the SUMO E1 provide mechanistic insights into SUMO activation and E2 recruitment to E1. EMBO J. 24, 439–451 (2005).
Sugimoto, Y. et al. A metagenomic strategy for harnessing the chemical repertoire of the human microbiome. Science https://doi.org/10.1126/science.aax9176 (2019).
Balaich, J. et al. The human microbiome encodes resistance to the antidiabetic drug acarbose. Nature 600, 110–115 (2021).
Parsek, M. R. & Greenberg, E. P. Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling mechanism involved in associations with higher organisms. Proc. Natl Acad. Sci. USA 97, 8789–8793 (2000).
Brameyer, S., Kresovic, D., Bode, H. B. & Heermann, R. Dialkylresorcinols as bacterial signaling molecules. Proc. Natl Acad. Sci. USA 112, 572–577 (2015).
Kelly, R. C. et al. The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA. Nat. Chem. Biol. 5, 891–895 (2009).
Wang, L. H. et al. A bacterial cell-cell communication signal with cross-kingdom structural analogues. Mol. Microbiol. 51, 903–912 (2004).
Zhou, S. et al. Molecular basis for control of antibiotic production by a bacterial hormone. Nature 590, 463–467 (2021).
Wellington, S. & Greenberg, E. P. Quorum sensing signal selectivity and the potential for interspecies cross talk. mBio https://doi.org/10.1128/mBio.00146-19 (2019).
Wilbanks, L. E. et al. Synthesis of gamma-butyrolactone hormones enables understanding of natural product induction. ACS Chem. Biol. 18, 1624–1631 (2023).
Robes, J. M. D. et al. A conserved biosynthetic gene cluster is regulated by quorum sensing in a shipworm symbiont. Appl. Environ. Microbiol. 88, e0027022 (2022).
Li, X. H. & Lee, J. H. Quorum sensing-dependent post-secretional activation of extracellular proteases in Pseudomonas aeruginosa. J. Biol. Chem. 294, 19635–19644 (2019).
Chang, S. C. & Lee, C. Y. Quorum-sensing regulator OpaR directly represses seven protease genes in Vibrio parahaemolyticus. Front. Microbiol. 11, 534692 (2020).
Steinmoen, H., Knutsen, E. & Havarstein, L. S. Induction of natural competence in Streptococcus pneumoniae triggers lysis and DNA release from a subfraction of the cell population. Proc. Natl Acad. Sci. USA 99, 7681–7686 (2002).
Rued, B. E. et al. Quorum sensing in Streptococcus mutans regulates production of tryglysin, a novel RaS-RiPP antimicrobial compound. mBio https://doi.org/10.1128/mBio.02688-20 (2021).
Alves, J. A., Leal, F. C., Previato-Mello, M. & da Silva Neto, J. F. A quorum sensing-regulated type VI secretion system containing multiple nonredundant VgrG proteins is required for interbacterial competition in Chromobacterium violaceum. Microbiol. Spectr. 10, e0157622 (2022).
Majerczyk, C., Schneider, E. & Greenberg, E. P. Quorum sensing control of type VI secretion factors restricts the proliferation of quorum-sensing mutants. eLife 5, e14712 (2016).
Qian, G. et al. Proteomic analysis reveals novel extracellular virulence-associated proteins and functions regulated by the diffusible signal factor (DSF) in Xanthomonas oryzae pv. oryzicola. J. Proteome Res. 12, 3327–3341 (2013).
Riedel, K. et al. N-acyl-l-homoserine lactone-mediated regulation of the lip secretion system in Serratia liquefaciens MG1. J. Bacteriol. 183, 1805–1809 (2001).
Schuster, M., Lostroh, C. P., Ogi, T. & Greenberg, E. P. Identification, timing, and signal specificity of Pseudomonas aeruginosa quorum-controlled genes: a transcriptome analysis. J. Bacteriol. 185, 2066–2079 (2003).
Patzelt, D. et al. You are what you talk: quorum sensing induces individual morphologies and cell division modes in Dinoroseobacter shibae. ISME J. 7, 2274–2286 (2013).
Huber, M. et al. An RNA sponge controls quorum sensing dynamics and biofilm formation in Vibrio cholerae. Nat. Commun. 13, 7585 (2022).
Waters, C. M., Lu, W., Rabinowitz, J. D. & Bassler, B. L. Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT. J. Bacteriol. 190, 2527–2536 (2008).
Huber, B. et al. The cep quorum-sensing system of Burkholderia cepacia H111 controls biofilm formation and swarming motility. Microbiology 147, 2517–2528 (2001).
Hammer, B. K. & Bassler, B. L. Quorum sensing controls biofilm formation in Vibrio cholerae. Mol. Microbiol. 50, 101–104 (2003).
Patzelt, D. et al. Gene flow across genus barriers—conjugation of Dinoroseobacter shibae’s 191-kb killer plasmid into Phaeobacter inhibens and AHL-mediated expression of type IV secretion systems. Front. Microbiol. 7, 742 (2016).
Eberhard, A. et al. Structural identification of autoinducer of Photobacterium fischeri luciferase. Biochemistry 20, 2444–2449 (1981).
Trifinopoulos, J., Nguyen, L. T., von Haeseler, A. & Minh, B. Q. W-IQ-TREE: a fast online phylogenetic tool for maximum likelihood analysis. Nucleic Acids Res. 44, W232–W235 (2016).
Tamura, K., Stecher, G. & Kumar, S. MEGA11: Molecular Evolutionary Genetics Analysis version 11. Mol. Biol. Evol. 38, 3022–3027 (2021).
Blin, K. et al. antiSMASH 7.0: new and improved predictions for detection, regulation, chemical structures and visualisation. Nucleic Acids Res. 51, W46–W50 (2023).
The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 486, 207–214 (2012).
Lloyd-Price, J. et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature 550, 61–66 (2017).
Nielsen, H. B. et al. Identification and assembly of genomes and genetic elements in complex metagenomic samples without using reference genomes. Nat. Biotechnol. 32, 822–828 (2014).
Qin, J. et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490, 55–60 (2012).
Brito, I. L. et al. Mobile genes in the human microbiome are structured from global to individual scales. Nature 535, 435–439 (2016).
Feng, Q. et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat. Commun. 6, 6528 (2015).
Thomas, A. M. et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat. Med. 25, 667–678 (2019).
Wirbel, J. et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat. Med. 25, 679–689 (2019).
Yachida, S. et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat. Med. 25, 968–976 (2019).
Yu, J. et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut 66, 70 (2017).
Schirmer, M. et al. Linking the human gut microbiome to inflammatory cytokine production capacity. Cell 167, 1125–1136 (2016).
Weng, Y. J. et al. Correlation of diet, microbiota and metabolite networks in inflammatory bowel disease. J. Dig. Dis. 20, 447–459 (2019).
Zeevi, D. et al. Personalized nutrition by prediction of glycemic responses. Cell 163, 1079–1094 (2015).
Abu-Ali, G. S. et al. Metatranscriptome of human faecal microbial communities in a cohort of adult men. Nat. Microbiol. 3, 356–366 (2018).
Schirmer, M. et al. Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat. Microbiol. 3, 337–346 (2018).
Lloyd-Price, J. et al. Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature 569, 655–662 (2019).
Peterson, S. N. et al. Functional expression of dental plaque microbiota. Front. Cell Infect. Microbiol. 4, 108 (2014).
Benitez-Paez, A., Belda-Ferre, P., Simon-Soro, A. & Mira, A. Microbiota diversity and gene expression dynamics in human oral biofilms. BMC Genom. 15, 311 (2014).
Jorth, P. et al. Metatranscriptomics of the human oral microbiome during health and disease. mBio 5, e01012-14 (2014).
Szafranski, S. P. et al. Functional biomarkers for chronic periodontitis and insights into the roles of Prevotella nigrescens and Fusobacterium nucleatum; a metatranscriptome analysis. npj Biofilms Microbiomes 1, 15017 (2015).
Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357–359 (2012).
Edgar, R. C. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 32, 1792–1797 (2004).
Shkoporov, A. N. et al. Long-term persistence of crAss-like phage crAss001 is associated with phase variation in Bacteroides intestinalis. BMC Biol. 19, 163 (2021).
Procter, J. B. et al. Alignment of biological sequences with Jalview. Methods Mol. Biol. 2231, 203–224 (2021).
Engler, C., Kandzia, R. & Marillonnet, S. A one pot, one step, precision cloning method with high throughput capability. PLoS ONE 3, e3647 (2008).
Alvarez, B., Secades, P., McBride, M. J. & Guijarro, J. A. Development of genetic techniques for the psychrotrophic fish pathogen Flavobacterium psychrophilum. Appl. Environ. Microbiol. 70, 581–587 (2004).
Goodman, A. L. et al. Identifying genetic determinants needed to establish a human gut symbiont in its habitat. Cell Host Microbe 6, 279–289 (2009).
Li, Z., Ioca, L. P., He, R. & Donia, M. S. Natural diversifying evolution of nonribosomal peptide synthetases in a defensive symbiont reveals nonmodular functional constraints. PNAS Nexus 3, pgae384 (2024).
Marfey, P. Determination of d-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. Carlsberg Res. Commun. 49, 591–596 (1984).
Shi, T. T. et al. Design, synthesis and properties investigation of Nα-acylation lysine based derivatives. RSC Adv. 9, 7587–7593 (2019).
Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D 67, 235–242 (2011).
Evans, P. R. & Murshudov, G. N. How good are my data and what is the resolution? Acta Crystallogr. D 69, 1204–1214 (2013).
Kabsch, W. Xds. Acta Crystallogr. D 66, 125–132 (2010).
McCoy, A. J. Solving structures of protein complexes by molecular replacement with Phaser. Acta Crystallogr. D 63, 32–41 (2007).
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126–2132 (2004).
Meng, E. C. et al. UCSF ChimeraX: tools for structure building and analysis. Protein Sci. 32, e4792 (2023).
Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).
van Kempen, M. et al. Fast and accurate protein structure search with Foldseek. Nat. Biotechnol. 42, 243–246 (2024).
Thompson, J. D., Gibson, T. J. & Higgins, D. G. Multiple sequence alignment using ClustalW and ClustalX. Curr. Protoc. Bioinform. https://doi.org/10.1002/0471250953.bi0203s00 (2002).
Churchill, M. E. & Chen, L. Structural basis of acyl-homoserine lactone-dependent signaling. Chem. Rev. 111, 68–85 (2011).
