Skip to main content
SpringerLink
Log in

Bacterial DNA Methylation and Methylomes

  • Chapter
  • First Online:
DNA Methyltransferases - Role and Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 945))

Abstract

Formation of C5-methylcytosine, N4-methylcytosine, and N6-methyladenine in bacterial genomes is postreplicative and involves transfer of a methyl group from S-adenosyl-methionine to a base embedded in a specific DNA sequence context. Most bacterial DNA methyltransferases belong to restriction-modification systems; in addition, “solitary” or “orphan” DNA methyltransferases are frequently found in the genomes of bacteria and phage. Base methylation can affect the interaction of DNA-binding proteins with their cognate sites, either by a direct effect (e.g., steric hindrance) or by changes in DNA topology. In both Alphaproteobacteria and Gammaproteobacteria, the roles of DNA base methylation are especially well known for N6-methyladenine, including control of chromosome replication, nucleoid segregation, postreplicative correction of DNA mismatches, cell cycle-coupled transcription, formation of bacterial cell lineages, and regulation of bacterial virulence. Technical procedures that permit genome-wide analysis of DNA methylation are nowadays expanding our knowledge of the extent, evolution, and physiological significance of bacterial DNA methylation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AdoMet:

S-Adenosyl-L-methionine

CcrM:

Cell cycle-regulated methylase

Cori:

Replication origin of the Caulobacter chromosome

CRISP-R:

Clustered regularly interspaced short palindromic repeats

IPD:

Interpulse duration

LD50 :

Median lethal dose

Mod:

Modification gene in restriction-modification systems

oriC:

Replication origin of the E. coli chromosome

SMALR:

Single-molecule modification analysis of long reads

SMRT:

Single-molecule real time

SPI-1:

Salmonella pathogenicity island 1

UAS:

Upstream regulatory region

VSP:

Very-short-patch

References

  • Albu RF, Jurkowski TP, Jeltsch A. The Caulobacter crescentus DNA-(adenine N6)-methyltransferase CcrM methylates DNA in a distributive manner. Nucleic Acids Res. 2011;40(4):1708–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Arber W. Genetic variation: molecular mechanisms and impact on microbial evolution. FEMS Microbiol Rev. 2000;24(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  • Arber W, Linn S. DNA modification and restriction. Annu Rev Biochem. 1969;38:467–500.

    Article  CAS  PubMed  Google Scholar 

  • Aya Castaneda Mdel R, Sarnacki SH, Noto Llana M, Lopez Guerra AG, Giacomodonato MN, Cerquetti MC. Dam methylation is required for efficient biofilm production in Salmonella enterica serovar Enteritidis. Int J Food Microbiol. 2015;193:15–22.

    Article  PubMed  CAS  Google Scholar 

  • Balbontin R, Rowley G, Pucciarelli MG, Lopez-Garrido J, Wormstone Y, Lucchini S, Garcia-Del Portillo F, Hinton JC, Casadesus J. DNA adenine methylation regulates virulence gene expression in Salmonella enterica serovar Typhimurium. J Bacteriol. 2006;188(23):8160–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banas JA, Biswas S, Zhu M. Effects of DNA methylation on expression of virulence genes in Streptococcus mutans. Appl Environ Microbiol. 2011;77(20):7236–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Beaulaurier J, Zhang XS, Zhu S, Sebra R, Rosenbluh C, Deikus G, Shen N, Munera D, Waldor MK, Chess A, Blaser MJ, Schadt EE, Fang G. Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes. Nat Commun. 2015;6:7438.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benkovic SJ, Baker SJ, Alley MR, Woo YH, Zhang YK, Akama T, Mao W, Baboval J, Rajagopalan PT, Wall M, Kahng LS, Tavassoli A, Shapiro L. Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH. J Med Chem. 2005;48(23):7468–76.

    Article  CAS  PubMed  Google Scholar 

  • Bergerat A, Guschlbauer W, Fazakerley GV. Allosteric and catalytic binding of S-adenosylmethionine to Escherichia coli DNA adenine methyltransferase monitored by 3H NMR. Proc Natl Acad Sci U S A. 1991;88(15):6394–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bertani G, Weigle JJ. Host controlled variation in bacterial viruses. J Bacteriol. 1953;65(2):113–21.

    Google Scholar 

  • Bhaya D, Davison M, Barrangou R. CRISPR-Cas systems in bacteria and archaea: versatile small RNAs for adaptive defense and regulation. Annu Rev Genet. 2012;45:273–97.

    Article  CAS  Google Scholar 

  • Blakeway LV, Power PM, Jen FE, Worboys SR, Boitano M, Clark TA, Korlach J, Bakaletz LO, Jennings MP, Peak IR, Seib KL. ModM DNA methyltransferase methylome analysis reveals a potential role for Moraxella catarrhalis phasevarions in otitis media. FASEB J. 2014;28(12):5197–207.

    Article  CAS  PubMed  Google Scholar 

  • Blow MJ, Clark TA, Daum CG, Deutschbauer AM, Fomenkov A, Fries R, Froula J, Kang DD, Malmstrom RR, Morgan RD, Posfai J, Singh K, Visel A, Wetmore K, Zhao Z, Rubin EM, Korlach J, Pennacchio LA, Roberts RJ. The epigenomic landscape of prokaryotes. PLoS Genet. 2016;12(2):e1005854.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Blyn LB, Braaten BA, Low DA. Regulation of pap pilin phase variation by a mechanism involving differential dam methylation states. EMBO J. 1990;9(12):4045–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Boye E, Løbner-Olesen A, Skarstad K. Limiting DNA replication to once and only once. EMBO Rep. 2000;1(6):479–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braaten BA, Nou X, Kaltenbach LS, Low DA. Methylation patterns in pap regulatory DNA control pyelonephritis-associated pili phase variation in E. coli. Cell. 1994;76(3):577–88.

    Article  CAS  PubMed  Google Scholar 

  • Braun RE, Wright A. DNA methylation differentially enhances the expression of one of the two E. coli dnaA promoters in vivo and in vitro. Mol Gen Genet. 1986;202(2):246–50.

    Article  CAS  PubMed  Google Scholar 

  • Broadbent SE, Balbontin R, Casadesus J, Marinus MG, van der Woude M. YhdJ, a nonessential CcrM-like DNA methyltransferase of Escherichia coli and Salmonella enterica. J Bacteriol. 2007;189(11):4325–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broadbent SE, Davies MR, van der Woude MW. Phase variation controls expression of Salmonella lipopolysaccharide modification genes by a DNA methylation-dependent mechanism. Mol Microbiol. 2010;77(2):337–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brunet YR, Bernard CS, Gavioli M, Lloubes R, Cascales E. An epigenetic switch involving overlapping Fur and DNA methylation optimizes expression of a type VI secretion gene cluster. PLoS Genet. 2011;7(7):e1002205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calmann MA, Marinus MG. Regulated expression of the Escherichia coli dam gene. J Bacteriol. 2003;185(16):5012–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Camacho EM, Casadesus J. Conjugal transfer of the virulence plasmid of Salmonella enterica is regulated by the leucine-responsive regulatory protein and DNA adenine methylation. Mol Microbiol. 2002;44(6):1589–98.

    Article  CAS  PubMed  Google Scholar 

  • Camacho EM, Casadesus J. Regulation of traJ transcription in the Salmonella virulence plasmid by strand-specific DNA adenine hemimethylation. Mol Microbiol. 2005;57(6):1700–18.

    Article  CAS  PubMed  Google Scholar 

  • Casadesus J, D’Ari R. Memory in bacteria and phage. Bioessays. 2002;24(6):512–8.

    Article  CAS  PubMed  Google Scholar 

  • Casadesus J, Low D. Epigenetic gene regulation in the bacterial world. Microbiol Mol Biol Rev. 2006;70(3):830–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Casadesus J, Low DA. Programmed heterogeneity: epigenetic mechanisms in bacteria. J Biol Chem. 2013;288(20):13929–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chao MC, Zhu S, Kimura S, Davis BM, Schadt EE, Fang G, Waldor MK. A cytosine methyltransferase modulates the cell envelope stress response in the cholera pathogen. PLoS Genet. 2015;11(11):e1005666.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen L, Paulsen DB, Scruggs DW, Banes MM, Reeks BY, Lawrence ML. Alteration of DNA adenine methylase (Dam) activity in Pasteurella multocida causes increased spontaneous mutation frequency and attenuation in mice. Microbiology. 2003;149:2283–90.

    Article  CAS  PubMed  Google Scholar 

  • Cheng X. Structure and function of DNA methyltransferases. Annu Rev Biophys Biomol Struct. 1995;24:293–318.

    Article  CAS  PubMed  Google Scholar 

  • Coffin SR, Reich NO. Modulation of Escherichia coli DNA methyltransferase activity by biologically derived GATC-flanking sequences. J Biol Chem. 2008;283(29):20106–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collier J. Epigenetic regulation of the bacterial cell cycle. Curr Opin Microbiol. 2009;12(6):722–9.

    Article  CAS  PubMed  Google Scholar 

  • Correnti J, Munster V, Chan T, Woude M. Dam-dependent phase variation of Ag43 in Escherichia coli is altered in a seqA mutant. Mol Microbiol. 2002;44(2):521–32.

    Article  CAS  PubMed  Google Scholar 

  • Cota I, Blanc-Potard AB, Casadesus J. STM2209-STM2208 (opvAB): a phase variation locus of Salmonella enterica involved in control of O-antigen chain length. PLoS One. 2012;7(5):e36863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cota I, Bunk B, Sproer C, Overmann J, Konig C, Casadesus J. OxyR-dependent formation of DNA methylation patterns in OpvABOFF and OpvABON cell lineages of Salmonella enterica. Nucleic Acids Res. 2016;44(8):3595–609. doi:10.1093/nar/gkv1483.

    Article  CAS  PubMed  Google Scholar 

  • Cota I, Sanchez-Romero MA, Hernandez SB, Pucciarelli MG, Garcia-Del Portillo F, Casadesus J. Epigenetic control of Salmonella enterica O-antigen chain length: A tradeoff between virulence and bacteriophage resistance. PLoS Genet. 2015;11(11):e1005667.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cullum J, Collins JF, Broda P. The spread of plasmids in model populations of Escherichia coli K12. Plasmid. 1978;1(4):545–56.

    Article  CAS  PubMed  Google Scholar 

  • Danese PN, Pratt LA, Dove SL, Kolter R. The outer membrane protein, antigen 43, mediates cell-to-cell interactions within Escherichia coli biofilms. Mol Microbiol. 2000;37(2):424–32.

    Article  CAS  PubMed  Google Scholar 

  • Davies MR, Broadbent SE, Harris SR, Thomson NR, van der Woude MW. Horizontally acquired glycosyltransferase operons drive salmonellae lipopolysaccharide diversity. PLoS Genet. 2013;9(6):e1003568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis BM, Chao MC, Waldor MK. Entering the era of bacterial epigenomics with single molecule real time DNA sequencing. Curr Opin Microbiol. 2013;16(2):192–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fälker S, Schilling J, Schmidt MA, Heusipp G. Overproduction of DNA adenine methyltransferase alters motility, invasion, and the lipopolysaccharide O-antigen composition of Yersinia enterocolitica. Infect Immun. 2007;75(10):4990–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fang G, Munera D, Friedman DI, Mandlik A, Chao MC, Banerjee O, Feng Z, Losic B, Mahajan MC, Jabado OJ, Deikus G, Clark TA, Luong K, Murray IA, Davis BM, Keren-Paz A, Chess A, Roberts RJ, Korlach J, Turner SW, Kumar V, Waldor MK, Schadt EE. Genome-wide mapping of methylated adenine residues in pathogenic Escherichia coli using single-molecule real-time sequencing. Nat Biotechnol. 2012;30(12):1232–9.

    Article  CAS  PubMed  Google Scholar 

  • Fioravanti A, Fumeaux C, Mohapatra SS, Bompard C, Brilli M, Frandi A, Castric V, Villeret V, Viollier PH, Biondi EG. DNA binding of the cell cycle transcriptional regulator GcrA depends on N6-adenosine methylation in Caulobacter crescentus and other Alphaproteobacteria. PLoS Genet. 2013;9(5):e1003541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flusberg BA, Webster DR, Lee JH, Travers KJ, Olivares EC, Clark TA, Korlach J, Turner SW. Direct detection of DNA methylation during single-molecule, real-time sequencing. Nat Methods. 2010;7(6):461–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fox KL, Dowideit SJ, Erwin AL, Srikhanta YN, Smith AL, Jennings MP. Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression. Nucleic Acids Res. 2007a;35(15):5242–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fox KL, Srikhanta YN, Jennings MP. Phase variable type III restriction-modification systems of host-adapted bacterial pathogens. Mol Microbiol. 2007b;65(6):1375–9.

    Article  CAS  PubMed  Google Scholar 

  • Furuta Y, Namba-Fukuyo H, Shibata TF, Nishiyama T, Shigenobu S, Suzuki Y, Sugano S, Hasebe M, Kobayashi I. Methylome diversification through changes in DNA methyltransferase sequence specificity. PLoS Genet. 2014;10(4):e1004272.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Garcia-Del Portillo F, Pucciarelli MG, Casadesus J. DNA adenine methylase mutants of Salmonella typhimurium show defects in protein secretion, cell invasion, and M cell cytotoxicity. Proc Natl Acad Sci U S A. 1999;96(20):11578–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giacomodonato MN, Sarnacki SH, Caccuri RL, Sordelli DO, Cerquetti MC. Host response to a dam mutant of Salmonella enterica serovar Enteritidis with a temperature-sensitive phenotype. Infect Immun. 2004;72(9):5498–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giacomodonato MN, Sarnacki SH, Llana MN, Cerquetti MC. Dam and its role in pathogenicity of Salmonella enterica. J Infect Dev Ctries. 2009a;3(7):484–90.

    Article  CAS  PubMed  Google Scholar 

  • Giacomodonato MN, Sarnacki SH, Llana MN, Garcia Cattaneo AS, Uzzau S, Rubino S, Cerquetti MC. Impaired synthesis and secretion of SopA in Salmonella Typhimurium dam mutants. FEMS Microbiol Lett. 2009b;292(1):71–7.

    Article  CAS  PubMed  Google Scholar 

  • Glickman B, van den Elsen P, Radman M. Induced mutagenesis in dam- mutants of Escherichia coli: a role for 6-methyladenine residues in mutation avoidance. Mol Gen Genet. 1978;163(3):307–12.

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez D, Collier J. DNA methylation by CcrM activates the transcription of two genes required for the division of Caulobacter crescentus. Mol Microbiol. 2013;88(1):203–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez D, Kozdon JB, McAdams HH, Shapiro L, Collier J. The functions of DNA methylation by CcrM in Caulobacter crescentus: a global approach. Nucleic Acids Res. 2014;42(6):3720–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haagmans W, van der Woude M. Phase variation of Ag43 in Escherichia coli: Dam-dependent methylation abrogates OxyR binding and OxyR-mediated repression of transcription. Mol Microbiol. 2000;35(4):877–87.

    Article  CAS  PubMed  Google Scholar 

  • Hale WB, van der Woude MW, Low DA. Analysis of nonmethylated GATC sites in the Escherichia coli chromosome and identification of sites that are differentially methylated in response to environmental stimuli. J Bacteriol. 1994;176(11):3438–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heithoff DM, Enioutina EI, Daynes RA, Sinsheimer RL, Low DA, Mahan MJ. Salmonella DNA adenine methylase mutants confer cross-protective immunity. Infect Immun. 2001;69:6725–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heithoff DM, Sinsheimer RL, Low DA, Mahan MJ. An essential role for DNA adenine methylation in bacterial virulence. Science. 1999;284(5416):967–70.

    Article  CAS  PubMed  Google Scholar 

  • Hénaut A, Rouxel T, Gleizes A, Moszer I, Danchin A. Uneven distribution of GATC motifs in the Escherichia coli chromosome, its plasmids and its phages. J Mol Biol. 1996;257(3):574–85.

    Article  PubMed  Google Scholar 

  • Henderson IR, Owen P. The major phase-variable outer membrane protein of Escherichia coli structurally resembles the immunoglobulin A1 protease class of exported protein and is regulated by a novel mechanism involving Dam and OxyR. J Bacteriol. 1999;181(7):2132–41.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Herman GE, Modrich P. Escherichia coli dam methylase. Physical and catalytic properties of the homogeneous enzyme. J Biol Chem. 1982;257(5):2605–12.

    CAS  PubMed  Google Scholar 

  • Hernday A, Krabbe M, Braaten B, Low D. Self-perpetuating epigenetic pili switches in bacteria. Proc Natl Acad Sci U S A. 2002;99:16470–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hernday AD, Braaten BA, Low DA. The mechanism by which DNA adenine methylase and PapI activate the pap epigenetic switch. Mol Cell. 2003;12(4):947–57.

    Article  CAS  PubMed  Google Scholar 

  • Heusipp G, Fälker S, Schmidt MA. DNA adenine methylation and bacterial pathogenesis. Int J Med Microbiol. 2007;297(1):1–7.

    Article  CAS  PubMed  Google Scholar 

  • Iyer RR, Pluciennik A, Burdett V, Modrich PL. DNA mismatch repair: functions and mechanisms. Chem Rev. 2006;106(2):302–23.

    Article  CAS  PubMed  Google Scholar 

  • Jakomin M, Chessa D, Baumler AJ, Casadesus J. Regulation of the Salmonella enterica std fimbrial operon by DNA adenine methylation, SeqA, and HdfR. J Bacteriol. 2008;190(22):7406–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeltsch A. Beyond Watson and Crick: DNA methylation and molecular enzymology of DNA methyltransferases. Chembiochem. 2002;3(4):274–93.

    Article  CAS  PubMed  Google Scholar 

  • Jeltsch A. Maintenance of species identity and controlling speciation of bacteria: a new function for restriction/modification systems? Gene. 2003;317(1–2):13–6.

    Article  CAS  PubMed  Google Scholar 

  • Joshi MC, Magnan D, Montminy TP, Lies M, Stepankiw N, Bates D. Regulation of sister chromosome cohesion by the replication fork tracking protein SeqA. PLoS Genet. 2013;9(8):e1003673.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kahng LS, Shapiro L. The CcrM DNA methyltransferase of Agrobacterium tumefaciens is essential, and its activity is cell-cycle regulated. J Bacteriol. 2001;183(10):3065–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kahramanoglou C, Prieto AI, Khedkar S, Haase B, Gupta A, Benes V, Fraser GM, Luscombe NM, Seshasayee AS. Genomics of DNA cytosine methylation in Escherichia coli reveals its role in stationary phase transcription. Nat Commun. 2012;3:886.

    Article  PubMed  CAS  Google Scholar 

  • Kaltenbach LS, Braaten BA, Low DA. Specific binding of PapI to Lrp-pap DNA complexes. J Bacteriol. 1995;177(22):6449–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaminska R, van der Woude MW. Establishing and maintaining sequestration of Dam target sites for phase variation of agN43 in Escherichia coli. J Bacteriol. 2010;192(7):1937–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim JS, Li J, Barnes IH, Baltzegar DA, Pajaniappan M, Cullen TW, Trent MS, Burns CM, Thompson SA. Role of the Campylobacter jejuni Cj1461 DNA methyltransferase in regulating virulence characteristics. J Bacteriol. 2008;190(19):6524–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim M, Ryu S. Spontaneous and transient defence against bacteriophage by phase-variable glucosylation of O-antigen in Salmonella enterica serovar Typhimurium. Mol Microbiol. 2012;86(2):411–25.

    Article  CAS  PubMed  Google Scholar 

  • Kozdon JB, Melfi MD, Luong K, Clark TA, Boitano M, Wang S, Zhou B, Gonzalez D, Collier J, Turner SW, Korlach J, Shapiro L, McAdams HH. Global methylation state at base-pair resolution of the Caulobacter genome throughout the cell cycle. Proc Natl Acad Sci U S A. 2013;110(48):E4658–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krebes J, Morgan RD, Bunk B, Sproer C, Luong K, Parusel R, Anton BP, Konig C, Josenhans C, Overmann J, Roberts RJ, Korlach J, Suerbaum S. The complex methylome of the human gastric pathogen Helicobacter pylori. Nucleic Acids Res. 2014;42(4):2415–32.

    Article  CAS  PubMed  Google Scholar 

  • Kucherer C, Lother H, Kolling R, Schauzu MA, Messer W. Regulation of transcription of the chromosomal dnaA gene of Escherichia coli. Mol Gen Genet. 1985;205(1):115–21.

    Article  Google Scholar 

  • Kumar R, Mukhopadhyay AK, Ghosh P, Rao DN. Comparative transcriptomics of H. pylori strains AM5, SS1 and their hpyAVIBM deletion mutants: possible roles of cytosine methylation. PLoS One. 2012;7(8):e42303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee WC, Anton BP, Wang S, Baybayan P, Singh S, Ashby M, Chua EG, Tay CY, Thirriot F, Loke MF, Goh KL, Marshall BJ, Roberts RJ, Vadivelu J. The complete methylome of Helicobacter pylori UM032. BMC Genomics. 2015;16:424.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lluch-Senar M, Luong K, Llorens-Rico V, Delgado J, Fang G, Spittle K, Clark TA, Schadt E, Turner SW, Korlach J, Serrano L. Comprehensive methylome characterization of Mycoplasma genitalium and Mycoplasma pneumoniae at single-base resolution. PLoS Genet. 2013;9(1):e1003191.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Løbner-Olesen A, Boye E, Marinus MG. Expression of the Escherichia coli dam gene. Mol Microbiol. 1992;6(13):1841–51.

    Article  PubMed  Google Scholar 

  • Løbner-Olesen A, Skovgaard O, Marinus MG. Dam methylation: coordinating cellular processes. Curr Op Microbiol. 2005;8:154–60.

    Article  CAS  Google Scholar 

  • Loenen WA, Dryden DT, Raleigh EA, Wilson GG, Murray NE. Highlights of the DNA cutters: a short history of the restriction enzymes. Nucleic Acids Res. 2014;42(1):3–19.

    Article  CAS  PubMed  Google Scholar 

  • Loenen WA, Raleigh EA. The other face of restriction: modification-dependent enzymes. Nucleic Acids Res. 2014;42(1):56–69.

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Garrido J, Casadesus J. Regulation of Salmonella enterica pathogenicity island 1 by DNA adenine methylation. Genetics. 2010;184(3):637–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lopez-Garrido J, Casadesus J. Crosstalk between virulence loci: regulation of Salmonella enterica pathogenicity island 1 (SPI-1) by products of the std fimbrial operon. PLoS One. 2012;7(1):e30499.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Low DA, Casadesus J. Clocks and switches: bacterial gene regulation by DNA adenine methylation. Curr Opin Microbiol. 2008;11(2):106–12.

    Article  CAS  PubMed  Google Scholar 

  • Lu M, Campbell JL, Boye E, Kleckner N. SeqA: a negative modulator of replication initiation in E. coli. Cell. 1994;77(3):413–26.

    Article  CAS  PubMed  Google Scholar 

  • Luthje P, Brauner A. Ag43 promotes persistence of uropathogenic Escherichia coli isolates in the urinary tract. J Clin Microbiol. 2010;48(6):2316–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Marinus MG. Methylation of DNA. In: Neidhardt FC et al. editors. Escherichia coli and Salmonella. Cellular and molecular biology. 2nd ed. Washington, DC: ASM Press; 1996. p. 782–91.

    Google Scholar 

  • Marinus MG, Casadesus J. Roles of DNA adenine methylation in host-pathogen interactions: mismatch repair, transcriptional regulation, and more. FEMS Microbiol Rev. 2009;33(3):488–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marinus MG, Morris NR. Biological function for 6-methyladenine residues in the DNA of Escherichia coli K12. J Mol Biol. 1974;85(2):309–22.

    Article  CAS  PubMed  Google Scholar 

  • Marinus MG, Poteete A, Arraj JA. Correlation of DNA adenine methylase activity with spontaneous mutability in Escherichia coli K-12. Gene. 1984;28(1):123–5.

    Article  CAS  PubMed  Google Scholar 

  • Mashhoon N, Carroll M, Pruss C, Eberhard J, Ishikawa S, Estabrook RA, Reich N. Functional characterization of Escherichia coli DNA adenine methyltransferase, a novel target for antibiotics. J Biol Chem. 2004;259:52075–81.

    Article  CAS  Google Scholar 

  • Mashhoon N, Pruss C, Carroll M, Johnson PH, Reich N. Selective inhibitors of bacterial DNA adenine methyltransferases. J Biomol Screen. 2006;11:497–506.

    Article  CAS  PubMed  Google Scholar 

  • Messer W, Bellekes U, Lother H. Effect of dam methylation on the activity of the E. coli replication origin, oriC. EMBO J. 1985;4(5):1327–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Militello KT, Mandarano AH, Varechtchouk O, Simon RD. Cytosine DNA methylation influences drug resistance in Escherichia coli through increased sugE expression. FEMS Microbiol Lett. 2013;350(1):100–6.

    Article  PubMed  CAS  Google Scholar 

  • Mohapatra SS, Fioravanti A, Biondi EG. DNA methylation in Caulobacter and other Alphaproteobacteria during cell cycle progression. Trends Microbiol. 2014;22:528–35.

    Article  CAS  PubMed  Google Scholar 

  • Mohler VL, Heithoff DM, Mahan MJ, Hornitzky MA, Thomson PC, House JK. Development of a novel in-water vaccination protocol for DNA adenine methylase deficient Salmonella enterica serovar Typhimurium vaccine in adult sheep. Vaccine. 2012;30(8):1481–91.

    Article  CAS  PubMed  Google Scholar 

  • Mott ML, Berger JM. DNA replication initiation: mechanisms and regulation in bacteria. Nat Rev Microbiol. 2007;5(5):343–54.

    Article  CAS  PubMed  Google Scholar 

  • Murray IA, Clark TA, Morgan RD, Boitano M, Anton BP, Luong K, Fomenkov A, Turner SW, Korlach J, Roberts RJ. The methylomes of six bacteria. Nucleic Acids Res. 2012;40(22):11450–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naito T, Kusano K, Kobayashi I. Selfish behavior of restriction-modification systems. Science. 1995;267(5199):897–9.

    Article  CAS  PubMed  Google Scholar 

  • Oshima T, Wada C, Kawagoe Y, Ara T, Maeda M, Masuda Y, Hiraga S, Mori H. Genome-wide analysis of deoxyadenosine methyltransferase-mediated control of gene expression in Escherichia coli. Mol Microbiol. 2002;45(3):673–95.

    Article  CAS  PubMed  Google Scholar 

  • Peterson KR, Wertman KF, Mount DW, Marinus MG. Viability of Escherichia coli K-12 DNA adenine methylase (dam) mutants requires increased expression of specific genes in the SOS regulon. Mol Gen Genet. 1985;201(1):14–9.

    Article  CAS  PubMed  Google Scholar 

  • Peterson SN, Reich NO. GATC flanking sequences regulate Dam activity: evidence for how Dam specificity may influence pap expression. J Mol Biol. 2006;355(3):459–72.

    Article  CAS  PubMed  Google Scholar 

  • Pirone-Davies C, Hoffmann M, Roberts RJ, Muruvanda T, Timme RE, Strain E, Luo Y, Payne J, Luong K, Song Y, Tsai YC, Boitano M, Clark TA, Korlach J, Evans PS, Allard MW. Genome-wide methylation patterns in Salmonella enterica subsp. enterica serovars. PLoS One. 2015;10(4):e0123639.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Poole A, Penny D, Sjoberg BM. Confounded cytosine! Tinkering and the evolution of DNA. Nat Rev Mol Cell Biol. 2001;2(2):147–51.

    Article  CAS  PubMed  Google Scholar 

  • Pucciarelli MG, Prieto AI, Casadesus J, Garcia-del Portillo F. Envelope instability in DNA adenine methylase mutants of Salmonella enterica. Microbiology. 2002;148(4):1171–82.

    Article  CAS  PubMed  Google Scholar 

  • Pukkila PJ, Peterson J, Herman G, Modrich P, Meselson M. Effects of high levels of DNA adenine methylation on methyl-directed mismatch repair in Escherichia coli. Genetics. 1983;104(4):571–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ratel D, Ravanat JL, Charles MP, Platet N, Breuillaud L, Lunardi J, Berger F, Wion D. Undetectable levels of N6-methyl adenine in mouse DNA: cloning and analysis of PRED28, a gene coding for a putative mammalian DNA adenine methyltransferase. FEBS Lett. 2006;580(13):3179–84.

    Article  CAS  PubMed  Google Scholar 

  • Ringquist S, Smith CL. The Escherichia coli chromosome contains specific, unmethylated dam and dcm sites. Proc Natl Acad Sci U S A. 1992;89(10):4539–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roberts D, Hoopes BC, McClure WR, Kleckner N. IS10 transposition is regulated by DNA adenine methylation. Cell. 1985;43(1):117–30.

    Article  CAS  PubMed  Google Scholar 

  • Robertson GT, Reisenauer A, Wright R, Jensen RB, Jensen A, Shapiro L, Roop II RM. The Brucella abortus CcrM DNA methyltransferase is essential for viability, and its overexpression attenuates intracellular replication in murine macrophages. J Bacteriol. 2000;182(12):3482–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanchez-Romero MA, Cota I, Casadesus J. DNA methylation in bacteria: from the methyl group to the methylome. Curr Opin Microbiol. 2015;25:9–16.

    Article  CAS  PubMed  Google Scholar 

  • Shell SS, Prestwich EG, Baek SH, Shah RR, Sassetti CM, Dedon PC, Fortune SM. DNA methylation impacts gene expression and ensures hypoxic survival of Mycobacterium tuberculosis. PLoS Pathog. 2013;9(7):e1003419.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srikhanta YN, Dowideit SJ, Edwards JL, Falsetta ML, Wu HJ, Harrison OB, Fox KL, Seib KL, Maguire TL, Wang AH, Maiden MC, Grimmond SM, Apicella MA, Jennings MP. Phasevarions mediate random switching of gene expression in pathogenic Neisseria. PLoS Pathog. 2009;5(4):e1000400.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Srikhanta YN, Fox KL, Jennings MP. The phasevarion: phase variation of type III DNA methyltransferases controls coordinated switching in multiple genes. Nat Rev Microbiol. 2010;8(3):196–206.

    Article  CAS  PubMed  Google Scholar 

  • Srikhanta YN, Maguire TL, Stacey KJ, Grimmond SM, Jennings MP. The phasevarion: a genetic system controlling coordinated, random switching of expression of multiple genes. Proc Natl Acad Sci U S A. 2005;102(15):5547–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephens C, Reisenauer A, Wright R, Shapiro L. A cell cycle-regulated bacterial DNA methyltransferase is essential for viability. Proc Natl Acad Sci U S A. 1996;93(3):1210–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sternberg N, Sauer B, Hoess R, Abremski K. Bacteriophage P1 cre gene and its regulatory region. Evidence for multiple promoters and for regulation by DNA methylation. J Mol Biol. 1986;187(2):197–212.

    Article  CAS  PubMed  Google Scholar 

  • Tavazoie S, Church GM. Quantitative whole-genome analysis of DNA-protein interactions by in vivo methylase protection in E. coli. Nat Biotechnol. 1998;16(6):566–71.

    Article  CAS  PubMed  Google Scholar 

  • Torreblanca J, Casadesus J. DNA adenine methylase mutants of Salmonella typhimurium and a novel dam-regulated locus. Genetics. 1996;144(1):15–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Urig S, Gowher H, Hermann A, Beck C, Fatemi M, Humeny A, Jeltsch A. The Escherichia coli dam DNA methyltransferase modifies DNA in a highly processive reaction. J Mol Biol. 2002;319(5):1085–96.

    Article  CAS  PubMed  Google Scholar 

  • van der Woude M, Braaten B, Low D. Epigenetic phase variation of the pap operon in Escherichia coli. Trends Microbiol. 1996;4(1):5–9.

    Article  PubMed  Google Scholar 

  • van der Woude M, Hale WB, Low DA. Formation of DNA methylation patterns: nonmethylated GATC sequences in gut and pap operons. J Bacteriol. 1998;180(22):5913–20.

    PubMed  PubMed Central  Google Scholar 

  • van der Woude MW. Re-examining the role and random nature of phase variation. FEMS Microbiol Lett. 2006;254(2):190–7.

    Article  PubMed  CAS  Google Scholar 

  • van der Woude MW. Phase variation: how to create and coordinate population diversity. Curr Opin Microbiol. 2011;14(2):205–11.

    Article  PubMed  CAS  Google Scholar 

  • van der Woude MW, Bäumler AJ. Phase and antigenic variation in bacteria. Clin Microbiol Rev. 2004;17(3):581–611.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vanyushin BF, Belozersky AN, Kokurina NA, Kadirova DX. 5-methylcytosine and 6-methylamino-purine in bacterial DNA. Nature. 1968;218(5146):1066–7.

    Article  CAS  PubMed  Google Scholar 

  • Vanyushin BF, Buryanov YI, Belozersky AN. Distribution of N6-methyladenine in DNA of T2 phage and its host Escherichia coli B. Nat New Biol. 1971;230(1):25–7.

    Article  CAS  PubMed  Google Scholar 

  • Vasu K, Nagaraja V. Diverse functions of restriction-modification systems in addition to cellular defense. Microbiol Mol Biol Rev. 2013;77(1):53–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waldminghaus T, Skarstad K. The Escherichia coli SeqA protein. Plasmid. 2009;61(3):141–50.

    Article  CAS  PubMed  Google Scholar 

  • Waldron DE, Owen P, Dorman CJ. Competitive interaction of the OxyR DNA-binding protein and the Dam methylase at the antigen 43 gene regulatory region in Escherichia coli. Mol Microbiol. 2002;44(2):509–20.

    Article  CAS  PubMed  Google Scholar 

  • Wallecha A, Correnti J, Munster V, van der Woude M. Phase variation of Ag43 is independent of the oxidation state of OxyR. J Bacteriol. 2003;185(7):2203–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wallecha A, Munster V, Correnti J, Chan T, van der Woude M. Dam- and OxyR-dependent phase variation of agN43: essential elements and evidence for a new role of DNA methylation. J Bacteriol. 2002;184(12):3338–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang MX, Church GM. A whole genome approach to in vivo DNA-protein interactions in E. coli. Nature. 1992;360(6404):606–10.

    Article  CAS  PubMed  Google Scholar 

  • Watson Jr ME, Jarisch J, Smith AL. Inactivation of deoxyadenosine methyltransferase (dam) attenuates Haemophilus influenzae virulence. Mol Microbiol. 2004;53(2):651–64.

    Article  CAS  PubMed  Google Scholar 

  • Wilson GG, Murray NE. Restriction and modification systems. Annu Rev Genet. 1991;25:585–627. doi:10.1146/annurev.ge.25.120191.003101.

    Article  CAS  PubMed  Google Scholar 

  • Wion D, Casadesus J. N6-methyl-adenine: an epigenetic signal for DNA-protein interactions. Nat Rev Microbiol. 2006;4(3):183–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wright R, Stephens C, Shapiro L. The CcrM DNA methyltransferase is widespread in the alpha subdivision of proteobacteria, and its essential functions are conserved in Rhizobium meliloti and Caulobacter crescentus. J Bacteriol. 1997;179(18):5869–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

I thank Ignacio Cota, María A. Sánchez-Romero, and Lucía García-Pastor for discussions and Modesto Carballo, Laura Navarro, and Cristina Reyes (CITIUS) for assistance. Research in my laboratory is supported by grants BIO2013-44220-R from the Ministerio de Economía y Competitividad of Spain (MINECO) and the European Regional Fund, PCIN-2015-131 by MINECO and Infect-ERA, and CVI-5879 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain.

Author information

Authors and Affiliations

  1. Departamento de Genética, Universidad de Sevilla, Apartado 1095, Seville, 41080, Spain

    Josep Casadesús

Authors
  1. Josep Casadesús
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Josep Casadesús .

Editor information

Editors and Affiliations

  1. Institut für Biochemie, Universität Stuttgart, Stuttgart, Germany

    Albert Jeltsch

  2. BioMed X Innovation Center, Heidelberg, Germany

    Renata Z. Jurkowska

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Casadesús, J. (2016). Bacterial DNA Methylation and Methylomes. In: Jeltsch, A., Jurkowska, R. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 945. Springer, Cham. https://doi.org/10.1007/978-3-319-43624-1_3

Download citation

Publish with us

Policies and ethics

Search

Navigation