摘要
EpigenomicsVol. 14, No. 2 CommentaryChallenges in elucidating bacteria–host epigenetic dynamicsValakunja Nagaraja & Prakruti R SinghValakunja Nagaraja*Author for correspondence: Tel.: +91 80 2360 0668; E-mail Address: vraj@iisc.ac.inDepartment of Microbiology & Cell Biology, Indian Institute of Science, Bangalore, 560012, IndiaJawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, 560064, IndiaSearch for more papers by this author & Prakruti R SinghDepartment of Microbiology & Cell Biology, Indian Institute of Science, Bangalore, 560012, IndiaSearch for more papers by this authorPublished Online:22 Oct 2021https://doi.org/10.2217/epi-2021-0357AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: chromatin remodelingepigenetic modifiersepigeneticshistone acetylationhistone methylationnucleoid-associated proteinsPTMPapers of special note have been highlighted as: • of interest; •• of considerable interestReferences1. Becker PB, Workman JL. Nucleosome remodeling and epigenetics. Cold Spring Harb. Perspect. Biol. 5(9), 1–19 (2013).Crossref, Google Scholar2. Allis CD, Jenuwein T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 17(8), 487–500 (2016).Crossref, Medline, CAS, Google Scholar3. Murn J, Shi Y. The winding path of protein methylation research: milestones and new frontiers. Nat. Rev. Mol. Cell Biol. 18(8), 517–527 (2017).Crossref, Medline, CAS, Google Scholar4. Dillon SC, Dorman CJ. Bacterial nucleoid-associated proteins, nucleoid structure and gene expression. Nat. Rev. Microbiol. 8, 185 (2010). • An authoritative overview describing the diverse function of nucleoid-associated proteins (NAPs) in shaping the bacterial nucleoid.Crossref, Medline, CAS, Google Scholar5. Hu L, Kong W, Yang D, Han Q, Guo L, Shi Y. Threonine phosphorylation fine-tunes the regulatory activity of histone-like nucleoid structuring protein in Salmonella transcription. Front. Microbiol. 10, 1515 (2019).Crossref, Medline, Google Scholar6. Carabetta VJ, Greco TM, Cristea IM, Dubnau D. YfmK is an Nε-lysine acetyltransferase that directly acetylates the histone-like protein HBsu in Bacillus subtilis. Proc. Natl Acad. Sci. USA 116(9), 3752–3757 (2019).Crossref, Medline, CAS, Google Scholar7. Dilweg IW, Dame RT. Post-translational modification of nucleoidassociated proteins: an extra layer of functional modulation in bacteria? Biochem. Soc. Trans. 46(5), 1381–1392 (2018).Crossref, Medline, CAS, Google Scholar8. Kapopoulou A, Lew JM, Cole ST. The MycoBrowser portal: a comprehensive and manually annotated resource for mycobacterial genomes. Tuberculosis 91(1), 8–13 (2011).Crossref, Medline, CAS, Google Scholar9. Hentchel KL, Escalante-Semerena JC. Acylation of biomolecules in Prokaryotes: a widespread strategy for the control of biological function and metabolic stress. Microbiol. Mol. Biol. Rev. 79(3), 321–346 (2015).Crossref, Medline, Google Scholar10. Bhowmick T, Ghosh S, Dixit K et al. Targeting mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors. Nat. Commun. 5(1), 4124 (2014). •• First example of bacterial NAP targeted by small-molecule inhibitors employing structure-based drug design. The inhibitors of Mycobacterium tuberculosis (Mtb) HU alter nucleoid dynamics impacting gene expression and killing Mtb.Crossref, Medline, CAS, Google Scholar11. Ghosh S, Padmanabhan B, Anand C, Nagaraja V. Lysine acetylation of the Mycobacterium tuberculosis HU protein modulates its DNA binding and genome organization. Mol. Microbiol. 100(4), 577–588 (2016).Crossref, Medline, CAS, Google Scholar12. Anand C, Santoshi M, Singh PR, Nagaraja V. Rv0802c is an acyltransferase that succinylates and acetylates Mycobacterium tuberculosis nucleoid-associated protein HU. Microbiology 167(7), 001058 (2021).Crossref, CAS, Google Scholar13. Kim KH, An DR, Song J et al. Mycobacterium tuberculosis Eis protein initiates suppression of host immune responses by acetylation of DUSP16/MKP-7. Proc. Natl Acad. Sci. USA 109(20), 7729–7734 (2012). • Mtb acetyltransferase EIS inhibits autophagy and phagosome maturation in infected macrophages by acetylating DUSP16/MKP-7 and supresses host immune responses for intracellular survival.Crossref, Medline, CAS, Google Scholar14. Hamon MA, Cossart P. Histone modifications and chromatin remodeling during bacterial infections. Cell Host Microbe 4(2), 100–109 (2008). •• This review illustrates a number of strategies employed by various bacterial pathogens in altering the host chromatin.Crossref, Medline, CAS, Google Scholar15. Cabezas-Cruz A, Alberdi P, Ayllón N et al. Anaplasma phagocytophilum increases the levels of histone modifying enzymes to inhibit cell apoptosis and facilitate pathogen infection in the tick vector Ixodes scapularis. Epigenetics 11(4), 303–319 (2016).Crossref, Medline, Google Scholar16. Silmon de Monerri NC, Kim K. Pathogens hijack the epigenome: a new twist on host-pathogen interactions. Am. J. Pathol. 184(4), 897–911 (2014). • Highlights the long-lasting epigenetic changes induced by pathogens upon infection in host and non-host cells.Crossref, Medline, Google Scholar17. Rolando M, Sanulli S, Rusniok C et al. Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication. Cell Host Microbe 13(4), 395–405 (2013). •• A secretory methyltransferase of L. pneumophila enters the host nucleus and uniquely adds a repressive mark by trimethylating K14 of histone H3. The addition of the mark alters the host gene expression giving survival advantage to the bacteria.Crossref, Medline, CAS, Google Scholar18. Yaseen I, Kaur P, Nandicoori VK, Khosla S. Mycobacteria modulate host epigenetic machinery by Rv1988 methylation of a non-tail arginine of histone H3. Nat. Commun. 6(1), 8922 (2015). • The authors suggest Rv1988 to be a mycobacterial virulence factor. It methylates histone H3 at H3R42 and perturbs the first line of defence against mycobacteria.Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByRNA polymerase efficiently transcribes through DNA ‐scaffolded, cooperative bacteriophage repressor complexes22 July 2022 | FEBS Letters, Vol. 596, No. 16 Vol. 14, No. 2 Follow us on social media for the latest updates Metrics Downloaded 76 times History Received 12 September 2021 Accepted 8 October 2021 Published online 22 October 2021 Published in print January 2022 Information© 2021 Future Medicine LtdKeywordschromatin remodelingepigenetic modifiersepigeneticshistone acetylationhistone methylationnucleoid-associated proteinsPTMFinancial & competing interests disclosureV Nagaraja is supported by grants from Department of Biotechnology, Science and Engineering Research Board – Department of Science & Technology, Government of India. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.No writing assistance was utilized in the production of this manuscript.PDF download