Molecules from the Microbiome

Literature Cited

1. 1. 

   Sender R, Fuchs S, Milo R 2016. Are we really vastly outnumbered? Revisiting the ratio of bacterial to host cells in humans. Cell 164:337–40
   [Google Scholar]
2. 2. 

   Qin J, Li R, Raes J, Arumugam M, Burgdorf KS et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464:59–65
   [Google Scholar]
3. 3. 

   Clemente JC, Ursell LK, Parfrey LW, Knight R. 2012. The impact of the gut microbiota on human health: an integrative view. Cell 148:1258–70
   [Google Scholar]
4. 4. 

   Zheng D, Liwinski T, Elinav E. 2020. Interaction between microbiota and immunity in health and disease. Cell Res 30:492–506
   [Google Scholar]
5. 5. 

   Hooper LV. 2004. Bacterial contributions to mammalian gut development. Trends Microbiol 12:129–34
   [Google Scholar]
6. 6. 

   Tang WHW, Li DY, Hazen SL. 2019. Dietary metabolism, the gut microbiome, and heart failure. Nat. Rev. Cardiol. 16:137–54
   [Google Scholar]
7. 7. 

   Yadav M, Verma MK, Chauhan NS. 2018. A review of metabolic potential of human gut microbiome in human nutrition. Arch. Microbiol. 200:203–17
   [Google Scholar]
8. 8. 

   Lee W-J, Hase K. 2014. Gut microbiota–generated metabolites in animal health and disease. Nat. Chem. Biol. 10:416–24
   [Google Scholar]
9. 9. 

   Koppel N, Maini Rekdal V, Balskus EP 2017. Chemical transformation of xenobiotics by the human gut microbiota. Science 356:eaag2770
   [Google Scholar]
10. 10. 

    Powell N, Walker MM, Talley NJ. 2017. The mucosal immune system: master regulator of bidirectional gut–brain communications. Nat. Rev. Gastroenterol. Hepatol. 14:143–59
    [Google Scholar]
11. 11. 

    Jorde LB, Wooding SP. 2004. Genetic variation, classification and ‘race.’. Nat. Genet. 36:S28–33
    [Google Scholar]
12. 12. 

    Huttenhower C, Gevers D, Knight R, Abubucker S, Badger JH et al. 2012. Structure, function and diversity of the healthy human microbiome. Nature 486:207–14
    [Google Scholar]
13. 13. 

    Blumberg R, Powrie F. 2012. Microbiota, disease, and back to health: a metastable journey. Sci. Transl. Med. 4:137rv7
    [Google Scholar]
14. 14. 

    Byrd AL, Segre JA. 2016. Adapting Koch's postulates. Science 351:224–26
    [Google Scholar]
15. 15. 

    Falkow S. 1988. Molecular Koch's postulates applied to microbial pathogenicity. Rev. Infect. Dis. 10:S274–76
    [Google Scholar]
16. 16. 

    Chen H, Nwe P-K, Yang Y, Rosen CE, Bielecka AA et al. 2019. A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology. Cell 177:1217–31 1218.
    [Google Scholar]
17. 17. 

    Fedorova ND, Moktali V, Medema MH 2012. Bioinformatics approaches and software for detection of secondary metabolic gene clusters. Fungal Secondary Metabolism: Methods and Protocols NP Keller, G Turner 23–45 Totowa, NJ: Humana Press
    [Google Scholar]
18. 18. 

    Medema MH, Fischbach MA. 2015. Computational approaches to natural product discovery. Nat. Chem. Biol. 11:639–48
    [Google Scholar]
19. 19. 

    Medema MH, Blin K, Cimermancic P, de Jager V, Zakrzewski P et al. 2011. antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res. 39:W339–46
    [Google Scholar]
20. 20. 

    Blin K, Shaw S, Steinke K, Villebro R, Ziemert N et al. 2019. antiSMASH 5.0: updates to the secondary metabolite genome mining pipeline. Nucleic Acids Res. 47:W81–87
    [Google Scholar]
21. 21. 

    Johnston CW, Skinnider MA, Dejong CA, Rees PN, Chen GM et al. 2016. Assembly and clustering of natural antibiotics guides target identification. Nat. Chem. Biol. 12:233–39
    [Google Scholar]
22. 22. 

    Skinnider MA, Dejong CA, Rees PN, Johnston CW, Li H et al. 2015. Genomes to natural products PRediction Informatics for Secondary Metabolomes (PRISM). Nucleic Acids Res. 43:9645–62
    [Google Scholar]
23. 23. 

    Skinnider MA, Merwin NJ, Johnston CW, Magarvey NA. 2017. PRISM 3: expanded prediction of natural product chemical structures from microbial genomes. Nucleic Acids Res. 45:W49–54
    [Google Scholar]
24. 24. 

    Cimermancic P, Medema, Marnix H, Claesen J, Kurita K et al. 2014. Insights into secondary metabolism from a global analysis of prokaryotic biosynthetic gene clusters. Cell 158:412–21
    [Google Scholar]
25. 25. 

    Vizcaino MI, Guo X, Crawford JM. 2014. Merging chemical ecology with bacterial genome mining for secondary metabolite discovery. J. Ind. Microbiol. Biotechnol. 41:285–99
    [Google Scholar]
26. 26. 

    Vallenet D, Engelen S, Mornico D, Cruveiller S, Fleury L et al. 2009. MicroScope: a platform for microbial genome annotation and comparative genomics. Database 2009.bap021
    [Google Scholar]
27. 27. 

    Ziemert N, Lechner A, Wietz M, Millán-Aguiñaga N, Chavarria KL, Jensen PR 2014. Diversity and evolution of secondary metabolism in the marine actinomycete genus Salinispora. PNAS 111:E1130–39
    [Google Scholar]
28. 28. 

    Ochman H, Lawrence JG, Groisman EA. 2000. Lateral gene transfer and the nature of bacterial innovation. Nature 405:299–304
    [Google Scholar]
29. 29. 

    Guo X, Crawford JM. 2014. An atypical orphan carbohydrate-NRPS genomic island encodes a novel lytic transglycosylase. Chem. Biol. 21:1271–77
    [Google Scholar]
30. 30. 

    Perez CE, Crawford JM. 2019. Characterization of a hybrid nonribosomal peptide–carbohydrate biosynthetic pathway in Photorhabdus luminescens. Biochemistry 58:1131–40
    [Google Scholar]
31. 31. 

    Park HB, Perez CE, Barber KW, Rinehart J, Crawford JM. 2017. Genome mining unearths a hybrid nonribosomal peptide synthetase-like-pteridine synthase biosynthetic gene cluster. eLife 6:e25229
    [Google Scholar]
32. 32. 

    Perez CE, Park HB, Crawford JM. 2018. Functional characterization of a condensation domain that links nonribosomal peptide and pteridine biosynthetic machineries in Photorhabdus luminescens. Biochemistry 57:354–61
    [Google Scholar]
33. 33. 

    Li JH, Oh J, Kienesberger S, Kim NY, Clarke DJ et al. 2020. Making and breaking leupeptin protease inhibitors in pathogenic gammaproteobacteria. Angew. Chem. Int. Ed. 59:17872–80
    [Google Scholar]
34. 34. 

    Miller IJ, Chevrette MG, Kwan JC. 2017. Interpreting microbial biosynthesis in the genomic age: biological and practical considerations. Mar. Drugs 15:165
    [Google Scholar]
35. 35. 

    Wilson MC, Piel J. 2013. Metagenomic approaches for exploiting uncultivated bacteria as a resource for novel biosynthetic enzymology. Chem. Biol. 20:636–47
    [Google Scholar]
36. 36. 

    Almeida A, Mitchell AL, Boland M, Forster SC, Gloor GB et al. 2019. A new genomic blueprint of the human gut microbiota. Nature 568:499–504
    [Google Scholar]
37. 37. 

    Sugimoto Y, Camacho FR, Wang S, Chankhamjon P, Odabas A et al. 2019. A metagenomic strategy for harnessing the chemical repertoire of the human microbiome. Science 366:eaax9176
    [Google Scholar]
38. 38. 

    Ellens KW, Christian N, Singh C, Satagopam VP, May P, Linster CL. 2017. Confronting the catalytic dark matter encoded by sequenced genomes. Nucleic Acids Res. 45:11495–514
    [Google Scholar]
39. 39. 

    Nannenga BL, Gonen T. 2019. The cryo-EM method microcrystal electron diffraction (MicroED). Nat. Methods 16:369–79
    [Google Scholar]
40. 40. 

    Tang X, Li J, Millán-Aguiñaga N, Zhang JJ, O'Neill EC et al. 2015. Identification of thiotetronic acid antibiotic biosynthetic pathways by target-directed genome mining. ACS Chem. Biol. 10:2841–49
    [Google Scholar]
41. 41. 

    Yan Y, Liu N, Tang Y. 2020. Recent developments in self-resistance gene directed natural product discovery. Nat. Prod. Rep. 37:879–92
    [Google Scholar]
42. 42. 

    Milshteyn A, Colosimo DA, Brady SF. 2018. Accessing bioactive natural products from the human microbiome. Cell Host Microbe 23:725–36
    [Google Scholar]
43. 43. 

    Cohen LJ, Kang H-S, Chu J, Huang Y-H, Gordon EA et al. 2015. Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist. PNAS 112:E4825–34
    [Google Scholar]
44. 44. 

    Lakhdari O, Cultrone A, Tap J, Gloux K, Bernard F et al. 2010. Functional metagenomics: a high throughput screening method to decipher microbiota-driven NF-κB modulation in the human gut. PLOS ONE 5:e13092
    [Google Scholar]
45. 45. 

    Zhang Q, Lenardo MJ, Baltimore D. 2017. 30 years of NF-κB: a blossoming of relevance to human pathobiology. Cell 168:37–57
    [Google Scholar]
46. 46. 

    Wang W-L, Xu S-Y, Ren Z-G, Tao L, Jiang J-W, Zheng S-S. 2015. Application of metagenomics in the human gut microbiome. World J. Gastroenterol. 21:803–14
    [Google Scholar]
47. 47. 

    Gabor EM, Alkema WBL, Janssen DB. 2004. Quantifying the accessibility of the metagenome by random expression cloning techniques. Environ. Microbiol. 6:879–86
    [Google Scholar]
48. 48. 

    Craig JW, Chang F-Y, Kim JH, Obiajulu SC, Brady SF. 2010. Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse Proteobacteria. Appl. Environ. Microbiol. 76:1633–41
    [Google Scholar]
49. 49. 

    Iqbal HA, Low-Beinart L, Obiajulu JU, Brady SF. 2016. Natural product discovery through improved functional metagenomics in Streptomyces. J. Am. Chem. Soc. 138:9341–44
    [Google Scholar]
50. 50. 

    Lagkouvardos I, Overmann J, Clavel T. 2017. Cultured microbes represent a substantial fraction of the human and mouse gut microbiota. Gut Microbes 8:493–503
    [Google Scholar]
51. 51. 

    Browne HP, Forster SC, Anonye BO, Kumar N, Neville BA et al. 2016. Culturing of ‘unculturable’ human microbiota reveals novel taxa and extensive sporulation. Nature 533:543–46
    [Google Scholar]
52. 52. 

    Guo C-J, Allen BM, Hiam KJ, Dodd D, Van Treuren W et al. 2019. Depletion of microbiome-derived molecules in the host using Clostridium genetics. Science 366:eaav1282
    [Google Scholar]
53. 53. 

    Lim B, Zimmermann M, Barry NA, Goodman AL. 2017. Engineered regulatory systems modulate gene expression of human commensals in the gut. Cell 169:547–58.e515
    [Google Scholar]
54. 54. 

    Tan G-Y, Liu T. 2017. Rational synthetic pathway refactoring of natural products biosynthesis in actinobacteria. Metab. Eng. 39:228–36
    [Google Scholar]
55. 55. 

    Wang G, Zhao Z, Ke J, Engel Y, Shi Y-M et al. 2019. CRAGE enables rapid activation of biosynthetic gene clusters in undomesticated bacteria. Nat. Microbiol. 4:2498–510
    [Google Scholar]
56. 56. 

    Covington BC, McLean JA, Bachmann BO. 2017. Comparative mass spectrometry-based metabolomics strategies for the investigation of microbial secondary metabolites. Nat. Product Rep. 34:6–24
    [Google Scholar]
57. 57. 

    Cameron SJS, Takáts Z. 2018. Mass spectrometry approaches to metabolic profiling of microbial communities within the human gastrointestinal tract. Methods 149:13–24
    [Google Scholar]
58. 58. 

    Lozano GL, Bravo JI, Garavito Diago MF, Park HB, Hurley A et al. 2019. Introducing THOR, a model microbiome for genetic dissection of community behavior. mBio 10:e02846–18
    [Google Scholar]
59. 59. 

    Quinn RA, Melnik AV, Vrbanac A, Fu T, Patras KA et al. 2020. Global chemical effects of the microbiome include new bile-acid conjugations. Nature 579:123–29
    [Google Scholar]
60. 60. 

    Patti GJ, Yanes O, Siuzdak G. 2012. Metabolomics: the apogee of the omics trilogy. Nat. Rev. Mol. Cell Biol. 13:263–69
    [Google Scholar]
61. 61. 

    Roume H, Muller EEL, Cordes T, Renaut J, Hiller K, Wilmes P. 2013. A biomolecular isolation framework for eco-systems biology. ISME J. 7:110–21
    [Google Scholar]
62. 62. 

    da Silva RR, Dorrestein PC, Quinn RA 2015. Illuminating the dark matter in metabolomics. PNAS 112:12549–50
    [Google Scholar]
63. 63. 

    Watrous J, Roach P, Alexandrov T, Heath BS, Yang JY et al. 2012. Mass spectral molecular networking of living microbial colonies. PNAS 109:E1743–52
    [Google Scholar]
64. 64. 

    De Vijlder T, Valkenborg D, Lemière F, Romijn EP, Laukens K, Cuyckens F. 2018. A tutorial in small molecule identification via electrospray ionization-mass spectrometry: the practical art of structural elucidation. Mass Spectrom. Rev. 37:607–29
    [Google Scholar]
65. 65. 

    Frank AM, Bandeira N, Shen Z, Tanner S, Briggs SP et al. 2008. Clustering millions of tandem mass spectra. J. Proteome Res. 7:113–22
    [Google Scholar]
66. 66. 

    Aron AT, Gentry EC, McPhail KL, Nothias L-F, Nothias-Esposito M et al. 2020. Reproducible molecular networking of untargeted mass spectrometry data using GNPS. Nat. Protoc. 15:1954–91
    [Google Scholar]
67. 67. 

    Yang JY, Sanchez LM, Rath CM, Liu X, Boudreau PD et al. 2013. Molecular networking as a dereplication strategy. J. Nat. Prod. 76:1686–99
    [Google Scholar]
68. 68. 

    Quinn RA, Nothias L-F, Vining O, Meehan M, Esquenazi E, Dorrestein PC. 2017. Molecular networking as a drug discovery, drug metabolism, and precision medicine strategy. Trends Pharmacol. Sci. 38:143–54
    [Google Scholar]
69. 69. 

    Fox Ramos AE, Evanno L, Poupon E, Champy P, Beniddir MA 2019. Natural products targeting strategies involving molecular networking: different manners, one goal. Nat. Prod. Rep. 36:960–80
    [Google Scholar]
70. 70. 

    Lamichhane S, Sen P, Dickens AM, Orešič M, Bertram HC. 2018. Gut metabolome meets microbiome: a methodological perspective to understand the relationship between host and microbe. Methods 149:3–12
    [Google Scholar]
71. 71. 

    Morton JT, Aksenov AA, Nothias LF, Foulds JR, Quinn RA et al. 2019. Learning representations of microbe–metabolite interactions. Nat. Methods 16:1306–14
    [Google Scholar]
72. 72. 

    Seyedsayamdost MR. 2019. Toward a global picture of bacterial secondary metabolism. J. Ind. Microbiol. Biotechnol. 46:301–11
    [Google Scholar]
73. 73. 

    Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS et al. 2013. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature. Nat. Prod. Rep. 30:108–60
    [Google Scholar]
74. 74. 

    Ortega MA, van der Donk WA. 2016. New insights into the biosynthetic logic of ribosomally synthesized and post-translationally modified peptide natural products. Cell Chem. Biol. 23:31–44
    [Google Scholar]
75. 75. 

    Donia MS, Cimermancic P, Schulze CJ, Wieland Brown LC, Martin J et al. 2014. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell 158:1402–14
    [Google Scholar]
76. 76. 

    Melby JO, Nard NJ, Mitchell DA. 2011. Thiazole/oxazole-modified microcins: complex natural products from ribosomal templates. Curr. Opin. Chem. Biol. 15:369–78
    [Google Scholar]
77. 77. 

    Vassiliadis G, Destoumieux-Garzón D, Lombard C, Rebuffat S, Peduzzi J. 2010. Isolation and characterization of two members of the siderophore-microcin family, microcins M and H47. Antimicrob. Agents Chemother. 54:288–97
    [Google Scholar]
78. 78. 

    Nolan EM, Walsh CT. 2008. Investigations of the MceIJ-catalyzed posttranslational modification of the microcin E492 C-terminus: linkage of ribosomal and nonribosomal peptides to form “Trojan horse” antibiotics. Biochemistry 47:9289–99
    [Google Scholar]
79. 79. 

    Severinov K, Nair SK. 2012. Microcin C: biosynthesis and mechanisms of bacterial resistance. Future Microbiol. 7:281–89
    [Google Scholar]
80. 80. 

    Sassone-Corsi M, Nuccio S-P, Liu H, Hernandez D, Vu CT et al. 2016. Microcins mediate competition among Enterobacteriaceae in the inflamed gut. Nature 540:280–83
    [Google Scholar]
81. 81. 

    Massip C, Branchu P, Bossuet-Greif N, Chagneau CV, Gaillard D et al. 2019. Deciphering the interplay between the genotoxic and probiotic activities of Escherichia coli Nissle 1917. PLOS Pathogens 15:e1008029
    [Google Scholar]
82. 82. 

    Patzer SI, Baquero MR, Bravo D, Moreno F, Hantke K. 2003. The colicin G, H and X determinants encode microcins M and H47, which might utilize the catecholate siderophore receptors FepA, Cir, Fiu and IroN. Microbiology 149:2557–70
    [Google Scholar]
83. 83. 

    Bowers AA, Acker MG, Koglin A, Walsh CT. 2010. Manipulation of thiocillin variants by prepeptide gene replacement: structure, conformation, and activity of heterocycle substitution mutants. J. Am. Chem. Soc. 132:7519–27
    [Google Scholar]
84. 84. 

    Wieland Brown LC, Acker MG, Clardy J, Walsh CT, Fischbach MA 2009. Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin. PNAS 106:2549–53
    [Google Scholar]
85. 85. 

    Just-Baringo X, Albericio F, Álvarez M 2014. Thiopeptide antibiotics: retrospective and recent advances. Mar. Drugs 12:317–51
    [Google Scholar]
86. 86. 

    Molloy EM, Cotter PD, Hill C, Mitchell DA, Ross RP. 2011. Streptolysin S-like virulence factors: the continuing sagA. Nat. Rev. Microbiol. 9:670–81
    [Google Scholar]
87. 87. 

    Lee SW, Mitchell DA, Markley AL, Hensler ME, Gonzalez D et al. 2008. Discovery of a widely distributed toxin biosynthetic gene cluster. PNAS 105:5879–84
    [Google Scholar]
88. 88. 

    Gonzalez DJ, Lee SW, Hensler ME, Markley AL, Dahesh S et al. 2010. Clostridiolysin S, a post-translationally modified biotoxin from Clostridium botulinum. J. Biol. Chem. 285:28220–28
    [Google Scholar]
89. 89. 

    Newman DJ, Cragg GM. 2020. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019. J. Nat. Prod. 83:770–803
    [Google Scholar]
90. 90. 

    Süssmuth RD, Mainz A. 2017. Nonribosomal peptide synthesis-principles and prospects. Angew. Chem. Int. Ed. 56:3770–821
    [Google Scholar]
91. 91. 

    Donia MS, Fischbach MA. 2015. Small molecules from the human microbiota. Science 349:1254766
    [Google Scholar]
92. 92. 

    Crosa JH, Walsh CT. 2002. Genetics and assembly line enzymology of siderophore biosynthesis in bacteria. Microbiol. . Mol. Biol. Rev. 66:223–49
    [Google Scholar]
93. 93. 

    Miethke M, Marahiel MA. 2007. Siderophore-based iron acquisition and pathogen control. Microbiol. Mol. Biol. Rev. 71:413–51
    [Google Scholar]
94. 94. 

    Caza M, Kronstad J. 2013. Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans. Front. Cell. Infect. Microbiol. 3:80
    [Google Scholar]
95. 95. 

    Kramer J, Özkaya Ö, Kümmerli R. 2020. Bacterial siderophores in community and host interactions. Nat. Rev. Microbiol. 18:152–63
    [Google Scholar]
96. 96. 

    Müller SI, Valdebenito M, Hantke K. 2009. Salmochelin, the long-overlooked catecholate siderophore of Salmonella. Biometals 22:691–95
    [Google Scholar]
97. 97. 

    Visser MB, Majumdar S, Hani E, Sokol PA. 2004. Importance of the ornibactin and pyochelin siderophore transport systems in Burkholderia cenocepacia lung infections. Infect. Immun. 72:2850–57
    [Google Scholar]
98. 98. 

    Valdebenito M, Crumbliss AL, Winkelmann G, Hantke K. 2006. Environmental factors influence the production of enterobactin, salmochelin, aerobactin, and yersiniabactin in Escherichia coli strain Nissle 1917. Int. J. Med. Microbiol. 296:513–20
    [Google Scholar]
99. 99. 

    Schubert S, Rakin A, Heesemann J. 2004. The Yersinia high-pathogenicity island (HPI): evolutionary and functional aspects. Int. J. Med. Microbiol. 294:83–94
    [Google Scholar]
100. 100. 

     Deriu E, Liu JZ, Pezeshki M, Edwards RA, Ochoa RJ et al. 2013. Probiotic bacteria reduce Salmonella typhimurium intestinal colonization by competing for iron. Cell Host Microbe 14:26–37
     [Google Scholar]
101. 101. 

     Raffatellu M, George MD, Akiyama Y, Hornsby MJ, Nuccio S-P et al. 2009. Lipocalin-2 resistance confers an advantage to Salmonella enterica serotype typhimurium for growth and survival in the inflamed intestine. Cell Host Microbe 5:476–86
     [Google Scholar]
102. 102. 

     Moynié L, Milenkovic S, Mislin GLA, Gasser V, Malloci G et al. 2019. The complex of ferric-enterobactin with its transporter from Pseudomonas aeruginosa suggests a two-site model. Nat. Commun. 10:3673
     [Google Scholar]
103. 103. 

     Zhu W, Winter MG, Spiga L, Hughes ER, Chanin R et al. 2020. Xenosiderophore utilization promotes Bacteroides thetaiotaomicron resilience during colitis. Cell Host Microbe 27:376–88.e378
     [Google Scholar]
104. 104. 

     Zipperer A, Konnerth MC, Laux C, Berscheid A, Janek D et al. 2016. Human commensals producing a novel antibiotic impair pathogen colonization. Nature 535:511–16
     [Google Scholar]
105. 105. 

     Joyce SA, Brachmann AO, Glazer I, Lango L, Schwär G et al. 2008. Bacterial biosynthesis of a multipotent stilbene. Angew. Chem. Int. Ed. 47:1942–45
     [Google Scholar]
106. 106. 

     Park HB, Goddard TN, Oh J, Patel J, Wei Z et al. 2020. Bacterial autoimmune drug metabolism transforms an immunomodulator into structurally and functionally divergent antibiotics. Angew. Chem. Int. Ed. 59:7871–80
     [Google Scholar]
107. 107. 

     Goddard TN, Patel J, Park HB, Crawford JM. 2020. Dimeric stilbene antibiotics target the bacterial cell wall in drug-resistant gram-positive pathogens. Biochemistry 59:1966–71
     [Google Scholar]
108. 108. 

     Faïs T, Delmas J, Barnich N, Bonnet R, Dalmasso G. 2018. Colibactin: more than a new bacterial toxin. Toxins 10:151
     [Google Scholar]
109. 109. 

     Wernke KM, Xue M, Tirla A, Kim CS, Crawford JM, Herzon SB. 2020. Structure and bioactivity of colibactin. Bioorg. Med. Chem. Lett. 30:127280
     [Google Scholar]
110. 110. 

     Taieb F, Petit C, Nougayrède JP, Oswald E 2016. The enterobacterial genotoxins: cytolethal distending toxin and colibactin. EcoSal Plus 7: https://doi.org/10.1128/ecosalplus.ESP-0008-2016
     [Crossref] [Google Scholar]
111. 111. 

     Johnson JR, Johnston B, Kuskowski MA, Nougayrede JP, Oswald E 2008. Molecular epidemiology and phylogenetic distribution of the Escherichia coli pks genomic island. J. Clin. Microbiol. 46:3906–11
     [Google Scholar]
112. 112. 

     Bossuet-Greif N, Vignard J, Taieb F, Mirey G, Dubois D et al. 2018. The colibactin genotoxin generates DNA interstrand cross-links in infected cells. mBio 9:e02393–17
     [Google Scholar]
113. 113. 

     Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrède J-P 2010. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. PNAS 107:11537–42
     [Google Scholar]
114. 114. 

     Nougayrède J-P, Homburg S, Taieb F, Boury M, Brzuszkiewicz E et al. 2006. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313:848–51
     [Google Scholar]
115. 115. 

     Secher T, Samba-Louaka A, Oswald E, Nougayrède J-P. 2013. Escherichia coli producing colibactin triggers premature and transmissible senescence in mammalian cells. PLOS ONE 8:e77157
     [Google Scholar]
116. 116. 

     Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM et al. 2012. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–23
     [Google Scholar]
117. 117. 

     Tomkovich S, Yang Y, Winglee K, Gauthier J, Mühlbauer M et al. 2017. Locoregional effects of microbiota in a preclinical model of colon carcinogenesis. Cancer Res. 77:2620–32
     [Google Scholar]
118. 118. 

     Buc E, Dubois D, Sauvanet P, Raisch J, Delmas J et al. 2013. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLOS ONE 8:e56964
     [Google Scholar]
119. 119. 

     Dejea CM, Fathi P, Craig JM, Boleij A, Taddese R et al. 2018. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science 359:592–97
     [Google Scholar]
120. 120. 

     Dziubańska-Kusibab PJ, Berger H, Battistini F, Bouwman BAM, Iftekhar A et al. 2020. Colibactin DNA-damage signature indicates mutational impact in colorectal cancer. Nat. Med. 26:1063–69
     [Google Scholar]
121. 121. 

     Pleguezuelos-Manzano C, Puschhof J, Rosendahl Huber A, van Hoeck A, Wood HM et al. 2020. Mutational signature in colorectal cancer caused by genotoxic pks⁺ E. coli. Nature 580:269–73
     [Google Scholar]
122. 122. 

     Xue M, Kim CS, Healy AR, Wernke KM, Wang Z et al. 2019. Structure elucidation of colibactin and its DNA cross-links. Science 365:eaax2685
     [Google Scholar]
123. 123. 

     Jiang Y, Stornetta A, Villalta PW, Wilson MR, Boudreau PD et al. 2019. Reactivity of an unusual amidase may explain colibactin's DNA cross-linking activity. J. Am. Chem. Soc. 141:11489–96
     [Google Scholar]
124. 124. 

     Xue M, Shine E, Wang W, Crawford JM, Herzon SB. 2018. Characterization of natural colibactin–nucleobase adducts by tandem mass spectrometry and isotopic labeling. Support for DNA alkylation by cyclopropane ring opening. Biochemistry 57:6391–94
     [Google Scholar]
125. 125. 

     Wilson MR, Jiang Y, Villalta PW, Stornetta A, Boudreau PD et al. 2019. The human gut bacterial genotoxin colibactin alkylates DNA. Science 363:eaar7785
     [Google Scholar]
126. 126. 

     Olier M, Marcq I, Salvador-Cartier C, Secher T, Dobrindt U et al. 2012. Genotoxicity of Escherichia coli Nissle 1917 strain cannot be dissociated from its probiotic activity. Gut Microbes 3:501–9
     [Google Scholar]
127. 127. 

     Nowrouzian FL, Oswald E 2012. Escherichia coli strains with the capacity for long-term persistence in the bowel microbiota carry the potentially genotoxic pks island. Microb. Pathog. 53:180–82
     [Google Scholar]
128. 128. 

     Tronnet S, Floch P, Lucarelli L, Gaillard D, Martin P et al. 2020. The genotoxin colibactin shapes gut microbiota in mice. mSphere 5:e00589–20
     [Google Scholar]
129. 129. 

     Wallenstein A, Rehm N, Brinkmann M, Selle M, Bossuet-Greif N et al. 2020. ClbR is the key transcriptional activator of colibactin gene expression in Escherichia coli. mSphere 5:00591–20
     [Google Scholar]
130. 130. 

     Putze J, Hennequin C, Nougayrède J-P, Zhang W, Homburg S et al. 2009. Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect. Immun. 77:4696–703
     [Google Scholar]
131. 131. 

     Martin P, Marcq I, Magistro G, Penary M, Garcie C et al. 2013. Interplay between siderophores and colibactin genotoxin biosynthetic pathways in Escherichia coli. PLOS Pathog. 9:e1003437
     [Google Scholar]
132. 132. 

     Healy AR, Wernke KM, Kim CS, Lees NR, Crawford JM, Herzon SB. 2019. Synthesis and reactivity of precolibactin 886. Nat. Chem. 11:890–98
     [Google Scholar]
133. 133. 

     Carlson-Banning KM, Sperandio V 2018. Enterohemorrhagic Escherichia coli outwits hosts through sensing small molecules. Curr. Opin. Microbiol. 41:83–88
     [Google Scholar]
134. 134. 

     Brotherton CA, Balskus EP. 2013. A prodrug resistance mechanism is involved in colibactin biosynthesis and cytotoxicity. J. Am. Chem. Soc. 135:3359–62
     [Google Scholar]
135. 135. 

     Bian X, Fu J, Plaza A, Herrmann J, Pistorius D et al. 2013. In vivo evidence for a prodrug activation mechanism during colibactin maturation. ChemBioChem 14:1194–97
     [Google Scholar]
136. 136. 

     Vizcaino MI, Engel P, Trautman E, Crawford JM. 2014. Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules. J. Am. Chem. Soc. 136:9244–47
     [Google Scholar]
137. 137. 

     Pérez-Berezo T, Pujo J, Martin P, Le Faouder P, Galano J-M et al. 2017. Identification of an analgesic lipopeptide produced by the probiotic Escherichia coli strain Nissle 1917. Nat. Commun. 8:1314
     [Google Scholar]
138. 138. 

     Barker HA. 1981. Amino acid degradation by anaerobic bacteria. Annu. Rev. Biochem. 50:23–40
     [Google Scholar]
139. 139. 

     Strandwitz P, Kim KH, Terekhova D, Liu JK, Sharma A et al. 2019. GABA-modulating bacteria of the human gut microbiota. Nat. Microbiol. 4:396–403
     [Google Scholar]
140. 140. 

     Schneditz G, Rentner J, Roier S, Pletz J, Herzog KAT et al. 2014. Enterotoxicity of a nonribosomal peptide causes antibiotic-associated colitis. PNAS 111:13181–86
     [Google Scholar]
141. 141. 

     von Tesmar A, Hoffmann M, Abou Fayad A, Hüttel S, Schmitt V et al. 2018. Biosynthesis of the Klebsiella oxytoca pathogenicity factor tilivalline: heterologous expression, in vitro biosynthesis, and inhibitor development. ACS Chem. Biol. 13:812–19
     [Google Scholar]
142. 142. 

     Dornisch E, Pletz J, Glabonjat RA, Martin F, Lembacher-Fadum C et al. 2017. Biosynthesis of the enterotoxic pyrrolobenzodiazepine natural product tilivalline. Angew. Chem. Int. Ed. 56:14753–57
     [Google Scholar]
143. 143. 

     Tse H, Gu Q, Sze KH, Chu IK, Kao RY et al. 2017. A tricyclic pyrrolobenzodiazepine produced by Klebsiella oxytoca is associated with cytotoxicity in antibiotic-associated hemorrhagic colitis. J. Biol. Chem. 292:19503–20
     [Google Scholar]
144. 144. 

     Högenauer C, Langner C, Beubler E, Lippe IT, Schicho R et al. 2006. Klebsiella oxytoca as a causative organism of antibiotic-associated hemorrhagic colitis. N. Engl. J. Med. 355:2418–26
     [Google Scholar]
145. 145. 

     Unterhauser K, Pöltl L, Schneditz G, Kienesberger S, Glabonjat RA et al. 2019. Klebsiella oxytoca enterotoxins tilimycin and tilivalline have distinct host DNA-damaging and microtubule-stabilizing activities. PNAS 116:3774–83
     [Google Scholar]
146. 146. 

     Alexander EM, Kreitler DF, Guidolin V, Hurben AK, Drake E et al. 2020. Biosynthesis, mechanism of action, and inhibition of the enterotoxin tilimycin produced by the opportunistic pathogen Klebsiella oxytoca. ACS Infect. Dis. 6:1976–97
     [Google Scholar]
147. 147. 

     Zollner-Schwetz I, Högenauer C, Joainig M, Weberhofer P, Gorkiewicz G et al. 2008. Role of Klebsiella oxytoca in antibiotic-associated diarrhea. Clin. Infect. Dis. 47:e74–78
     [Google Scholar]
148. 148. 

     Guo CJ, Chang FY, Wyche TP, Backus KM, Acker TM et al. 2017. Discovery of reactive microbiota-derived metabolites that inhibit host proteases. Cell 168:517–26.e518
     [Google Scholar]
149. 149. 

     Wyatt MA, Wang W, Roux CM, Beasley FC, Heinrichs DE et al. 2010. Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence. Science 329:294–96
     [Google Scholar]
150. 150. 

     Zimmermann M, Fischbach MA. 2010. A family of pyrazinone natural products from a conserved nonribosomal peptide synthetase in Staphylococcus aureus. Chem. Biol. 17:925–30
     [Google Scholar]
151. 151. 

     Kim CS, Gatsios A, Cuesta S, Lam YC, Wei Z et al. 2020. Characterization of autoinducer-3 structure and biosynthesis in E. coli. ACS Central Sci. 6:197–206
     [Google Scholar]
152. 152. 

     Sperandio V, Torres AG, Jarvis B, Nataro JP, Kaper JB 2003. Bacteria–host communication: the language of hormones. PNAS 100:8951–56
     [Google Scholar]
153. 153. 

     Papenfort K, Silpe JE, Schramma KR, Cong JP, Seyedsayamdost MR, Bassler BL. 2017. A Vibrio cholerae autoinducer-receptor pair that controls biofilm formation. Nat. Chem. Biol. 13:551–57
     [Google Scholar]
154. 154. 

     Rivera-Chávez F, Lopez CA, Bäumler AJ. 2017. Oxygen as a driver of gut dysbiosis. Free Radic. Biol. Med. 105:93–101
     [Google Scholar]
155. 155. 

     Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA et al. 2009. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. PNAS 106:3698–703
     [Google Scholar]
156. 156. 

     Dodd D, Spitzer MH, Van Treuren W, Merrill BD, Hryckowian AJ et al. 2017. A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites. Nature 551:648–52
     [Google Scholar]
157. 157. 

     Elsden SR, Hilton MG. 1978. Volatile acid production from threonine, valine, leucine and isoleucine by Clostridia. Arch. Microbiol. 117:165–72
     [Google Scholar]
158. 158. 

     Elsden SR, Hilton MG, Waller JM. 1976. The end products of the metabolism of aromatic amino acids by Clostridia. Arch. Microbiol. 107:283–88
     [Google Scholar]
159. 159. 

     Venkatesh M, Mukherjee S, Wang H, Li H, Sun K et al. 2014. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41:296–310
     [Google Scholar]
160. 160. 

     Cohen LJ, Esterhazy D, Kim S-H, Lemetre C, Aguilar RR et al. 2017. Commensal bacteria make GPCR ligands that mimic human signalling molecules. Nature 549:48–53
     [Google Scholar]
161. 161. 

     Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. 2019. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature 570:462–67
     [Google Scholar]
162. 162. 

     Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. 2019. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science 363:eaat9931
     [Google Scholar]