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Customizing Host Chromatin: a Bacterial Tale

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  • Authors: Michael Connor1, Laurence Arbibe2, Mélanie Hamon3
  • Editors: Pascale Cossart4, Craig R. Roy5, Philippe Sansonetti6
    Affiliations: 1: Institut Pasteur, G5 Chromatine et Infection, Paris, France; 2: INSERM U1151, CNRS UMR 8253, Institut Necker Enfants Malades, INEM Institute Department of Immunology, Infectiology and Hematology, Paris, France; 3: Institut Pasteur, G5 Chromatine et Infection, Paris, France; 4: Institut Pasteur, Paris, France; 5: Yale University School of Medicine, New Haven, Connecticut; 6: Institut Pasteur, Paris, France
  • Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0015-2019
  • Received 02 August 2018 Accepted 10 January 2019 Published 05 April 2019
  • Mélanie Hamon, [email protected]
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  • Abstract:

    Successful bacterial colonizers and pathogens have evolved with their hosts and have acquired mechanisms to customize essential processes that benefit their lifestyle. In large part, bacterial survival hinges on shaping the transcriptional signature of the host, a process regulated at the chromatin level. Modifications of chromatin, either on histone proteins or on DNA itself, are common targets during bacterium-host cross talk and are the focus of this article.

  • Citation: Connor M, Arbibe L, Hamon M. 2019. Customizing Host Chromatin: a Bacterial Tale. Microbiol Spectrum 7(2):BAI-0015-2019. doi:10.1128/microbiolspec.BAI-0015-2019.


1. Swygert SG, Peterson CL. 2014. Chromatin dynamics: interplay between remodeling enzymes and histone modifications. Biochim Biophys Acta 1839:728–736 http://dx.doi.org/10.1016/j.bbagrm.2014.02.013. [PubMed]
2. Clapier CR, Iwasa J, Cairns BR, Peterson CL. 2017. Mechanisms of action and regulation of ATP-dependent chromatin-remodelling complexes. Nat Rev Mol Cell Biol 18:407–422 http://dx.doi.org/10.1038/nrm.2017.26. [PubMed]
3. Strahl BD, Allis CD. 2000. The language of covalent histone modifications. Nature 403:41–45 http://dx.doi.org/10.1038/47412. [PubMed]
4. Barth TK, Imhof A. 2010. Fast signals and slow marks: the dynamics of histone modifications. Trends Biochem Sci 35:618–626 http://dx.doi.org/10.1016/j.tibs.2010.05.006. [PubMed]
5. Li B, Carey M, Workman JL. 2007. The role of chromatin during transcription. Cell 128:707–719 http://dx.doi.org/10.1016/j.cell.2007.01.015. [PubMed]
6. Hamon MA, Cossart P. 2008. Histone modifications and chromatin remodeling during bacterial infections. Cell Host Microbe 4:100–109 http://dx.doi.org/10.1016/j.chom.2008.07.009. [PubMed]
7. Saunders A, Core LJ, Lis JT. 2006. Breaking barriers to transcription elongation. Nat Rev Mol Cell Biol 7:557–567 http://dx.doi.org/10.1038/nrm1981. [PubMed]
8. Tremethick DJ. 2007. Higher-order structures of chromatin: the elusive 30 nm fiber. Cell 128:651–654 http://dx.doi.org/10.1016/j.cell.2007.02.008. [PubMed]
9. Kornberg RD, Lorch Y. 1999. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98:285–294 http://dx.doi.org/10.1016/S0092-8674(00)81958-3.
10. Kornberg RD. 1974. Chromatin structure: a repeating unit of histones and DNA. Science 184:868–871 http://dx.doi.org/10.1126/science.184.4139.868. [PubMed]
11. Thomas JO, Kornberg RD. 1975. An octamer of histones in chromatin and free in solution. Proc Natl Acad Sci USA 72:2626–2630 http://dx.doi.org/10.1073/pnas.72.7.2626. [PubMed]
12. Izzo A, Schneider R. 2016. The role of linker histone H1 modifications in the regulation of gene expression and chromatin dynamics. Biochim Biophys Acta 1859:486–495 http://dx.doi.org/10.1016/j.bbagrm.2015.09.003. [PubMed]
13. Sadakierska-Chudy A, Filip M. 2015. A comprehensive view of the epigenetic landscape. Part II: histone post-translational modification, nucleosome level, and chromatin regulation by ncRNAs. Neurotox Res 27:172–197 http://dx.doi.org/10.1007/s12640-014-9508-6. [PubMed]
14. Kouzarides T. 2007. Chromatin modifications and their function. Cell 128:693–705 http://dx.doi.org/10.1016/j.cell.2007.02.005. [PubMed]
15. Saccani S, Pantano S, Natoli G. 2001. Two waves of nuclear factor κB recruitment to target promoters. J Exp Med 193:1351–1360 http://dx.doi.org/10.1084/jem.193.12.1351. [PubMed]
16. Hargreaves DC, Horng T, Medzhitov R. 2009. Control of inducible gene expression by signal-dependent transcriptional elongation. Cell 138:129–145 http://dx.doi.org/10.1016/j.cell.2009.05.047. [PubMed]
17. Saccani S, Pantano S, Natoli G. 2002. p38-Dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat Immunol 3:69–75 http://dx.doi.org/10.1038/ni748. [PubMed]
18. Foster SL, Hargreaves DC, Medzhitov R. 2007. Gene-specific control of inflammation by TLR-induced chromatin modifications. Nature 447:972–978 CORRIGENDUM Nature 451:102 http://dx.doi.org/10.1038/nature05836.
19. Chang PV, Hao L, Offermanns S, Medzhitov R. 2014. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA 111:2247–2252 http://dx.doi.org/10.1073/pnas.1322269111. [PubMed]
20. Fellows R, Denizot J, Stellato C, Cuomo A, Jain P, Stoyanova E, Balázsi S, Hajnády Z, Liebert A, Kazakevych J, Blackburn H, Corrêa RO, Fachi JL, Sato FT, Ribeiro WR, Ferreira CM, Perée H, Spagnuolo M, Mattiuz R, Matolcsi C, Guedes J, Clark J, Veldhoen M, Bonaldi T, Vinolo MAR, Varga-Weisz P. 2018. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nat Commun 9:105 http://dx.doi.org/10.1038/s41467-017-02651-5. [PubMed]
21. Haberland M, Montgomery RL, Olson EN. 2009. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42 http://dx.doi.org/10.1038/nrg2485. [PubMed]
22. Yarbrough VL, Winkle S, Herbst-Kralovetz MM. 2015. Antimicrobial peptides in the female reproductive tract: a critical component of the mucosal immune barrier with physiological and clinical implications. Hum Reprod Update 21:353–377 http://dx.doi.org/10.1093/humupd/dmu065. [PubMed]
23. Bandyopadhaya A, Tsurumi A, Maura D, Jeffrey KL, Rahme LG. 2016. A quorum-sensing signal promotes host tolerance training through HDAC1-mediated epigenetic reprogramming. Nat Microbiol 1:16174 http://dx.doi.org/10.1038/nmicrobiol.2016.174. [PubMed]
24. Alto NM, Orth K. 2012. Subversion of cell signaling by pathogens. Cold Spring Harb Perspect Biol 4:a006114 http://dx.doi.org/10.1101/cshperspect.a006114. [PubMed]
25. Wang Y, Curry HM, Zwilling BS, Lafuse WP. 2005. Mycobacteria inhibition of IFN-gamma induced HLA-DR gene expression by up-regulating histone deacetylation at the promoter region in human THP-1 monocytic cells. J Immunol 174:5687–5694 http://dx.doi.org/10.4049/jimmunol.174.9.5687. [PubMed]
26. Pennini ME, Pai RK, Schultz DC, Boom WH, Harding CV. 2006. Mycobacterium tuberculosis 19-kDa lipoprotein inhibits IFN-gamma-induced chromatin remodeling of MHC2TA by TLR2 and MAPK signaling. J Immunol 176:4323–4330 http://dx.doi.org/10.4049/jimmunol.176.7.4323. [PubMed]
27. Cossart P. 2011. Illuminating the landscape of host-pathogen interactions with the bacterium Listeria monocytogenes. Proc Natl Acad Sci USA 108:19484–19491 http://dx.doi.org/10.1073/pnas.1112371108. [PubMed]
28. Ireton K, Payrastre B, Cossart P. 1999. The Listeria monocytogenes protein InlB is an agonist of mammalian phosphoinositide 3-kinase. J Biol Chem 274:17025–17032 http://dx.doi.org/10.1074/jbc.274.24.17025. [PubMed]
29. Bosse T, Ehinger J, Czuchra A, Benesch S, Steffen A, Wu X, Schloen K, Niemann HH, Scita G, Stradal TE, Brakebusch C, Rottner K. 2007. Cdc42 and phosphoinositide 3-kinase drive Rac-mediated actin polymerization downstream of c-Met in distinct and common pathways. Mol Cell Biol 27:6615–6628 http://dx.doi.org/10.1128/MCB.00367-07. [PubMed]
30. Eskandarian HA, Impens F, Nahori MA, Soubigou G, Coppée JY, Cossart P, Hamon MA. 2013. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341:1238858 http://dx.doi.org/10.1126/science.1238858. [PubMed]
31. Pereira JM, Chevalier C, Chaze T, Gianetto Q, Impens F, Matondo M, Cossart P, Hamon MA. 2018. Infection reveals a modification of SIRT2 critical for chromatin association. Cell Reports 23:1124–1137 http://dx.doi.org/10.1016/j.celrep.2018.03.116. [PubMed]
32. Kusters JG, van Vliet AHM, Kuipers EJ. 2006. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev 19:449–490 http://dx.doi.org/10.1128/CMR.00054-05. [PubMed]
33. Wang F, Meng W, Wang B, Qiao L. 2014. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 345:196–202 http://dx.doi.org/10.1016/j.canlet.2013.08.016. [PubMed]
34. Fehri LF, Rechner C, Janssen S, Mak TN, Holland C, Bartfeld S, Brüggemann H, Meyer TF. 2009. Helicobacter pylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation. Epigenetics 4:577–586 http://dx.doi.org/10.4161/epi.4.8.10217. [PubMed]
35. Ding SZ, Fischer W, Kaparakis-Liaskos M, Liechti G, Merrell DS, Grant PA, Ferrero RL, Crowe SE, Haas R, Hatakeyama M, Goldberg JB. 2010. Helicobacter pylori-induced histone modification, associated gene expression in gastric epithelial cells, and its implication in pathogenesis. PLoS One 5:e9875 http://dx.doi.org/10.1371/journal.pone.0009875. [PubMed]
36. Dal Peraro M, van der Goot FG. 2016. Pore-forming toxins: ancient, but never really out of fashion. Nat Rev Microbiol 14:77–92 http://dx.doi.org/10.1038/nrmicro.2015.3. [PubMed]
37. Hamon MA, Batsché E, Régnault B, Tham TN, Seveau S, Muchardt C, Cossart P. 2007. Histone modifications induced by a family of bacterial toxins. Proc Natl Acad Sci USA 104:13467–13472 CORRECTION Proc Natl Acad Sci USA 104:17555 http://dx.doi.org/10.1073/pnas.0702729104. [PubMed]
38. Hamon MA, Cossart P. 2011. K+ efflux is required for histone H3 dephosphorylation by Listeria monocytogenes listeriolysin O and other pore-forming toxins. Infect Immun 79:2839–2846 http://dx.doi.org/10.1128/IAI.01243-10. [PubMed]
39. Dortet L, Lombardi C, Cretin F, Dessen A, Filloux A. 2018. Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome. Nat Microbiol 3:378–386 http://dx.doi.org/10.1038/s41564-018-0109-7. [PubMed]
40. Yaseen I, Kaur P, Nandicoori VK, Khosla S. 2015. Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3. Nat Commun 6:8922 http://dx.doi.org/10.1038/ncomms9922. [PubMed]
41. The HC, Thanh DP, Holt KE, Thomson NR, Baker S. 2016. The genomic signatures of Shigella evolution, adaptation and geographical spread. Nat Rev Microbiol 14:235–250 http://dx.doi.org/10.1038/nrmicro.2016.10. [PubMed]
42. Arbibe L, Kim DW, Batsche E, Pedron T, Mateescu B, Muchardt C, Parsot C, Sansonetti PJ. 2007. An injected bacterial effector targets chromatin access for transcription factor NF-κB to alter transcription of host genes involved in immune responses. Nat Immunol 8:47–56 http://dx.doi.org/10.1038/ni1423. [PubMed]
43. Li H, Xu H, Zhou Y, Zhang J, Long C, Li S, Chen S, Zhou JM, Shao F. 2007. The phosphothreonine lyase activity of a bacterial type III effector family. Science 315:1000–1003 http://dx.doi.org/10.1126/science.1138960. [PubMed]
44. Harouz H, Rachez C, Meijer BM, Marteyn B, Donnadieu F, Cammas F, Muchardt C, Sansonetti P, Arbibe L. 2014. Shigella flexneri targets the HP1γ subcode through the phosphothreonine lyase OspF. EMBO J 33:2606–2622 http://dx.doi.org/10.15252/embj.201489244. [PubMed]
45. Lebreton A, Lakisic G, Job V, Fritsch L, Tham TN, Camejo A, Matteï PJ, Regnault B, Nahori MA, Cabanes D, Gautreau A, Ait-Si-Ali S, Dessen A, Cossart P, Bierne H. 2011. A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response. Science 331:1319–1321 http://dx.doi.org/10.1126/science.1200120. [PubMed]
46. Dillon SC, Zhang X, Trievel RC, Cheng X. 2005. The SET-domain protein superfamily: protein lysine methyltransferases. Genome Biol 6:227 http://dx.doi.org/10.1186/gb-2005-6-8-227. [PubMed]
47. Mujtaba S, Winer BY, Jaganathan A, Patel J, Sgobba M, Schuch R, Gupta YK, Haider S, Wang R, Fischetti VA. 2013. Anthrax SET protein: a potential virulence determinant that epigenetically represses NF-κB activation in infected macrophages. J Biol Chem 288:23458–23472 http://dx.doi.org/10.1074/jbc.M113.467696. [PubMed]
48. Pennini ME, Perrinet S, Dautry-Varsat A, Subtil A. 2010. Histone methylation by NUE, a novel nuclear effector of the intracellular pathogen Chlamydia trachomatis. PLoS Pathog 6:e1000995 http://dx.doi.org/10.1371/journal.ppat.1000995. [PubMed]
49. Rolando M, Sanulli S, Rusniok C, Gomez-Valero L, Bertholet C, Sahr T, Margueron R, Buchrieser C. 2013. Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication. Cell Host Microbe 13:395–405 http://dx.doi.org/10.1016/j.chom.2013.03.004. [PubMed]
50. Elwell C, Mirrashidi K, Engel J. 2016. Chlamydia cell biology and pathogenesis. Nat Rev Microbiol 14:385–400 http://dx.doi.org/10.1038/nrmicro.2016.30. [PubMed]
51. Liu S, Moayeri M, Leppla SH. 2014. Anthrax lethal and edema toxins in anthrax pathogenesis. Trends Microbiol 22:317–325 http://dx.doi.org/10.1016/j.tim.2014.02.012. [PubMed]
52. Pacis A, Tailleux L, Morin AM, Lambourne J, MacIsaac JL, Yotova V, Dumaine A, Danckaert A, Luca F, Grenier JC, Hansen KD, Gicquel B, Yu M, Pai A, He C, Tung J, Pastinen T, Kobor MS, Pique-Regi R, Gilad Y, Barreiro LB. 2015. Bacterial infection remodels the DNA methylation landscape of human dendritic cells. Genome Res 25:1801–1811 http://dx.doi.org/10.1101/gr.192005.115. [PubMed]
53. Sharma G, Upadhyay S, Srilalitha M, Nandicoori VK, Khosla S. 2015. The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding. Nucleic Acids Res 43:3922–3937 http://dx.doi.org/10.1093/nar/gkv261. [PubMed]
54. Niwa T, Tsukamoto T, Toyoda T, Mori A, Tanaka H, Maekita T, Ichinose M, Tatematsu M, Ushijima T. 2010. Inflammatory processes triggered by Helicobacter pylori infection cause aberrant DNA methylation in gastric epithelial cells. Cancer Res 70:1430–1440 http://dx.doi.org/10.1158/0008-5472.CAN-09-2755. [PubMed]
55. Woo HD, Fernandez-Jimenez N, Ghantous A, Degli Esposti D, Cuenin C, Cahais V, Choi IJ, Kim YI, Kim J, Herceg Z. 2018. Genome-wide profiling of normal gastric mucosa identifies Helicobacter pylori- and cancer-associated DNA methylome changes. Int J Cancer 143:597–609 http://dx.doi.org/10.1002/ijc.31381. [PubMed]
56. Shin CM, Kim N, Jung Y, Park JH, Kang GH, Kim JS, Jung HC, Song IS. 2010. Role of Helicobacter pylori infection in aberrant DNA methylation along multistep gastric carcinogenesis. Cancer Sci 101:1337–1346 http://dx.doi.org/10.1111/j.1349-7006.2010.01535.x. [PubMed]
57. Shin CM, Kim N, Jung Y, Park JH, Kang GH, Park WY, Kim JS, Jung HC, Song IS. 2011. Genome-wide DNA methylation profiles in noncancerous gastric mucosae with regard to Helicobacter pylori infection and the presence of gastric cancer. Helicobacter 16:179–188 http://dx.doi.org/10.1111/j.1523-5378.2011.00838.x. [PubMed]
58. Zhang Y, Zhang XR, Park JL, Kim JH, Zhang L, Ma JL, Liu WD, Deng DJ, You WC, Kim YS, Pan KF. 2016. Genome-wide DNA methylation profiles altered by Helicobacter pylori in gastric mucosa and blood leukocyte DNA. Oncotarget 7:37132–37144.
59. Pero R, Peluso S, Angrisano T, Tuccillo C, Sacchetti S, Keller S, Tomaiuolo R, Bruni CB, Lembo F, Chiariotti L. 2011. Chromatin and DNA methylation dynamics of Helicobacter pylori-induced COX-2 activation. Int J Med Microbiol 301:140–149 http://dx.doi.org/10.1016/j.ijmm.2010.06.009. [PubMed]
60. Maeda M, Moro H, Ushijima T. 2017. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway. Gastric Cancer 20(Suppl 1) :8–15 http://dx.doi.org/10.1007/s10120-016-0650-0. [PubMed]
61. Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M, Tamura G, Saito D, Sugimura T, Ichinose M, Ushijima T. 2006. High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 12:989–995 http://dx.doi.org/10.1158/1078-0432.CCR-05-2096. [PubMed]
62. Chumduri C, Gurumurthy RK, Zadora PK, Mi Y, Meyer TF. 2013. Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response. Cell Host Microbe 13:746–758 http://dx.doi.org/10.1016/j.chom.2013.05.010. [PubMed]
63. Vielfort K, Söderholm N, Weyler L, Vare D, Löfmark S, Aro H. 2013. Neisseria gonorrhoeae infection causes DNA damage and affects the expression of p21, p27 and p53 in non-tumor epithelial cells. J Cell Sci 126:339–347 http://dx.doi.org/10.1242/jcs.117721. [PubMed]
64. Strickertsson JA, Desler C, Martin-Bertelsen T, Machado AM, Wadstrøm T, Winther O, Rasmussen LJ, Friis-Hansen L. 2013. Enterococcus faecalis infection causes inflammation, intracellular oxphos-independent ROS production, and DNA damage in human gastric cancer cells. PLoS One 8:e63147 http://dx.doi.org/10.1371/journal.pone.0063147. [PubMed]
65. Samba-Louaka A, Pereira JM, Nahori MA, Villiers V, Deriano L, Hamon MA, Cossart P. 2014. Listeria monocytogenes dampens the DNA damage response. PLoS Pathog 10:e1004470 http://dx.doi.org/10.1371/journal.ppat.1004470. [PubMed]
66. Toller IM, Neelsen KJ, Steger M, Hartung ML, Hottiger MO, Stucki M, Kalali B, Gerhard M, Sartori AA, Lopes M, Müller A. 2011. Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response in its host cells. Proc Natl Acad Sci USA 108:14944–14949 http://dx.doi.org/10.1073/pnas.1100959108. [PubMed]
67. Lara-Tejero M, Galán JE. 2000. A bacterial toxin that controls cell cycle progression as a deoxyribonuclease I-like protein. Science 290:354–357 http://dx.doi.org/10.1126/science.290.5490.354. [PubMed]
68. Lara-Tejero M, Galán JE. 2001. CdtA, CdtB, and CdtC form a tripartite complex that is required for cytolethal distending toxin activity. Infect Immun 69:4358–4365 http://dx.doi.org/10.1128/IAI.69.7.4358-4365.2001. [PubMed]
69. Elwell CA, Dreyfus LA. 2000. DNase I homologous residues in CdtB are critical for cytolethal distending toxin-mediated cell cycle arrest. Mol Microbiol 37:952–963 http://dx.doi.org/10.1046/j.1365-2958.2000.02070.x. [PubMed]
70. Nešić D, Hsu Y, Stebbins CE. 2004. Assembly and function of a bacterial genotoxin. Nature 429:429–433 http://dx.doi.org/10.1038/nature02532. [PubMed]
71. Shenker BJ, Boesze-Battaglia K, Scuron MD, Walker LP, Zekavat A, Dlakić M. 2016. The toxicity of the Aggregatibacter actinomycetemcomitans cytolethal distending toxin correlates with its phosphatidylinositol-3,4,5-triphosphate phosphatase activity. Cell Microbiol 18:223–243 http://dx.doi.org/10.1111/cmi.12497. [PubMed]
72. Nishikubo S, Ohara M, Ueno Y, Ikura M, Kurihara H, Komatsuzawa H, Oswald E, Sugai M. 2003. An N-terminal segment of the active component of the bacterial genotoxin cytolethal distending toxin B (CDTB) directs CDTB into the nucleus. J Biol Chem 278:50671–50681 http://dx.doi.org/10.1074/jbc.M305062200. [PubMed]
73. Frisan T, Cortes-Bratti X, Chaves-Olarte E, Stenerlöw B, Thelestam M. 2003. The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA. Cell Microbiol 5:695–707 http://dx.doi.org/10.1046/j.1462-5822.2003.00311.x. [PubMed]
74. Elwell C, Chao K, Patel K, Dreyfus L. 2001. Escherichia coli CdtB mediates cytolethal distending toxin cell cycle arrest. Infect Immun 69:3418–3422 http://dx.doi.org/10.1128/IAI.69.5.3418-3422.2001. [PubMed]
75. Guidi R, Guerra L, Levi L, Stenerlöw B, Fox JG, Josenhans C, Masucci MG, Frisan T. 2013. Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response. Cell Microbiol 15:98–113 http://dx.doi.org/10.1111/cmi.12034. [PubMed]
76. Ge Z, Rogers AB, Feng Y, Lee A, Xu S, Taylor NS, Fox JG. 2007. Bacterial cytolethal distending toxin promotes the development of dysplasia in a model of microbially induced hepatocarcinogenesis. Cell Microbiol 9:2070–2080 http://dx.doi.org/10.1111/j.1462-5822.2007.00939.x. [PubMed]
77. Graillot V, Dormoy I, Dupuy J, Shay JW, Huc L, Mirey G, Vignard J. 2016. Genotoxicity of cytolethal distending toxin (CDT) on isogenic human colorectal cell lines: potential promoting effects for colorectal carcinogenesis. Front Cell Infect Microbiol 6:34 http://dx.doi.org/10.3389/fcimb.2016.00034. [PubMed]
78. Nougayrède J-P, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G, Buchrieser C, Hacker J, Dobrindt U, Oswald E. 2006. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313:848–851 http://dx.doi.org/10.1126/science.1127059. [PubMed]
79. Homburg S, Oswald E, Hacker J, Dobrindt U. 2007. Expression analysis of the colibactin gene cluster coding for a novel polyketide in Escherichia coli. FEMS Microbiol Lett 275:255–262 http://dx.doi.org/10.1111/j.1574-6968.2007.00889.x. [PubMed]
80. Vizcaino MI, Crawford JM. 2015. The colibactin warhead crosslinks DNA. Nat Chem 7:411–417 http://dx.doi.org/10.1038/nchem.2221. [PubMed]
81. Vizcaino MI, Engel P, Trautman E, Crawford JM. 2014. Comparative metabolomics and structural characterizations illuminate colibactin pathway-dependent small molecules. J Am Chem Soc 136:9244–9247 http://dx.doi.org/10.1021/ja503450q. [PubMed]
82. Bossuet-Greif N, Vignard J, Taieb F, Mirey G, Dubois D, Petit C, Oswald E, Nougayrède JP. 2018. The colibactin genotoxin generates DNA interstrand cross-links in infected cells. mBio 9:e02393-17 http://dx.doi.org/10.1128/mBio.02393-17. [PubMed]
83. Buc E, Dubois D, Sauvanet P, Raisch J, Delmas J, Darfeuille-Michaud A, Pezet D, Bonnet R. 2013. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLoS One 8:e56964 http://dx.doi.org/10.1371/journal.pone.0056964. [PubMed]
84. Netea MG, Joosten LA, Latz E, Mills KH, Natoli G, Stunnenberg HG, O’Neill LA, Xavier RJ. 2016. Trained immunity: A program of innate immune memory in health and disease. Science 352:aaf1098 http://dx.doi.org/10.1126/science.aaf1098. [PubMed]
85. Netea MG, Quintin J, van der Meer JW. 2011. Trained immunity: a memory for innate host defense. Cell Host Microbe 9:355–361 http://dx.doi.org/10.1016/j.chom.2011.04.006. [PubMed]
86. Netea MG, van Crevel R. 2014. BCG-induced protection: effects on innate immune memory. Semin Immunol 26:512–517 http://dx.doi.org/10.1016/j.smim.2014.09.006. [PubMed]
87. Grode L, Seiler P, Baumann S, Hess J, Brinkmann V, Nasser Eddine A, Mann P, Goosmann C, Bandermann S, Smith D, Bancroft GJ, Reyrat JM, van Soolingen D, Raupach B, Kaufmann SH. 2005. Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. J Clin Invest 115:2472–2479 http://dx.doi.org/10.1172/JCI24617. [PubMed]
88. Arts RJW, Moorlag SJCFM, Novakovic B, Li Y, Wang SY, Oosting M, Kumar V, Xavier RJ, Wijmenga C, Joosten LAB, Reusken CBEM, Benn CS, Aaby P, Koopmans MP, Stunnenberg HG, van Crevel R, Netea MG. 2018. BCG vaccination protects against experimental viral infection in humans through the induction of cytokines associated with trained immunity. Cell Host Microbe 23:89–100.e5 http://dx.doi.org/10.1016/j.chom.2017.12.010. [PubMed]

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Successful bacterial colonizers and pathogens have evolved with their hosts and have acquired mechanisms to customize essential processes that benefit their lifestyle. In large part, bacterial survival hinges on shaping the transcriptional signature of the host, a process regulated at the chromatin level. Modifications of chromatin, either on histone proteins or on DNA itself, are common targets during bacterium-host cross talk and are the focus of this article.

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Image of FIGURE 1

Nuclear effectors targeting histone marks. Secreted effectors from , , and translocate to the nucleus, where they directly act either upon the nucleosome itself (Rv1988 and OspF), bind chromatin readers to displace them (LntA), or bind chromatin readers to dephosphorylate them (OspF). Small black arrows around modifications indicate whether they are being deposited or removed.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0015-2019
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Image of FIGURE 2

SET domain effectors mediate histone methylation. Effectors of , , and contain the eukaryotic SET domain. Once translocated to the nucleus, these effectors target histones for direct methylation either globally or at specific residues. For and , this leads to repression of the host immune response and is thought to aid pathogen survival.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0015-2019
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Targeting host DNA. Genotoxins such as CDT and colibactin induce host DNA breaks through either DNase activity (CDT) or DNA cross-linking (colibactin). targets host DNA directly for methylation with Rv2966c at non-CpG elements or induces hypomethylation through an unknown effector at CpG islands.

Source: microbiolspec April 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0015-2019
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