Roles of DNA Adenine Methylation in Regulating Bacterial Gene Expression and Virulence

Low, David A.; Weyand, Nathan J.; Mahan, Michael J.

doi:10.1128/iai.69.12.7197-7204.2001

Cited by 302 publications

(279 citation statements)

References 95 publications

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“…A methylase, highly conserved but impaired restriction enzyme such as H. pylori hpyIM (11), is considered to broadly involve in regulation of a lot of the genes associated with H. pylori physiology including DNA replication, mismatch repair, cell cycle progression and/or expression of virulence determinants (15,21,22). Loss of hpyIM adenine methyltransferase that modifies at recognition sequence (CATG) altered expression of the stress-responsive dnaK operon (7).…”

Section: Discussionmentioning

confidence: 99%

Cell Elongation and Cell Death of Helicobacter pylori Is Modulated by the Disruption of cdrA (Cell Division‐Related Gene A)

Takeuchi

Nakazawa

Okamoto

et al. 2006

Microbiology and Immunology

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Helicobacter pylori (H. pylori), a gram-negative spiral bacterium, colonizes the human stomach and establishes a persistent infection associated with gastrointestinal inflammatory diseases including peptic gastric ulcer, duodenal ulcer, gastric cancer (31) and gastric mucosa-associated lymphoid tissue (MALT) lymphoma (2). The diversity or adaptive mutation in H. pylori genes like babA (1) generally alters the biological aspect of the microbe to response to individual conditions and eventually establishes a persistent infection in the human stomach. We previously reported that cdrA, a unique gene of H. pylori, has a repressive function on cell division. A wild-type strain HPK5 formed multinuclear filamentous cells in the early stationary phase and adopted coccoid forms in the stationary phase when grown in a high-salt level medium. On the other hand, a cdrA-disrupted mutant HPKT510 did not show such an abnormality and remained as short rods under the same conditions (30). By microarray analysis, the cdrA gene was found to be lost in 3 out of 4 colonies recovered

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Section: Discussionmentioning

confidence: 99%

Cell Elongation and Cell Death of Helicobacter pylori Is Modulated by the Disruption of cdrA (Cell Division‐Related Gene A)

Takeuchi

Nakazawa

Okamoto

et al. 2006

Microbiology and Immunology

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“…DNA methylation, which discriminates self from nonself in prokaryotes, is brought about either by solitary MTases or by MTases associated with REases. In bacteria, of the three kinds of DNA base modifications observed, m 5 C, m 4 C, and m 6 A, adenine-specific methylation has been well studied and shown to have diverse cellular roles (17)(18)(19)162). Functions carried out by this class of enzymes are self-versus-nonself discrimination during the restriction of phages, the downregulation or silencing of transposition events, the regulation of conjugation, the regulation of DNA replication initiation, cell cycle control, nucleoid reorganization, DNA mismatch repair, the transcriptional regulation of housekeeping and virulence genes, and posttranscriptional gene regulation (reviewed in references 162 and163).…”

Section: Functions Of Dna Adenine Methyltransferasesmentioning

confidence: 99%

“…In addition to the above-described four groups, a number of genomes are also known to encode MTases that are not associated with REases and are thus termed "orphan/solitary MTases." Examples of this group of enzymes are the N 6 -adenine MTases Dam and CcrM (cell cycle-regulated MTase) and the C-5-cytosine MTase Dcm (17)(18)(19). Interestingly, unlike the vast majority of REases, which are accompanied by MTases to protect the genomic DNA from selfdigestion, some of the rare-cutting REases, viz., R.PacI and R.PmeI, seem to be solitary enzymes with no cognate MTase (http: //rebase.neb.com/rebase/rebase.html) (20).…”

Section: Introductionmentioning

confidence: 99%

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

Vasu

Nagaraja

2013

Microbiol Mol Biol Rev

507

462

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SUMMARY Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population.

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“…However, some MTases exist alone, without an apparent cognate REase partner. These so-called "orphan" MTases include DNA adenine methylase (Dam), which modifies the adenine N-6 in the GATC motif, DNA cytosine methylase (Dcm), which methylates C-5 of the second cytosine in CC(A/T) GG sequences, and cell cycle-regulated methylase (CcrM), which methylates the N-6 of adenine in GANTC (N = A, T, C, or G) (8). Despite the absence of cognate REases, orphan MTases still confer immunity against the virulence of a parasitic R-M complex with the same target sites (9).…”

mentioning

confidence: 99%

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

Chen

Wang

Chen

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Explosive growth in the study of microbial epigenetics has revealed a diversity of chemical structures and biological functions of DNA modifications in restriction-modification (R-M) and basic genetic processes. Here, we describe the discovery of shared consensus sequences for two seemingly unrelated DNA modification systems, 6m A methylation and phosphorothioation (PT), in which sulfur replaces a nonbridging oxygen in the DNA backbone. Mass spectrometric analysis of DNA from Escherichia coli B7A and Salmonella enterica serovar Cerro 87, strains possessing PT-based R-M genes, revealed d(G PS 6m A) dinucleotides in the G PS 6m AAC consensus representing ∼5% of the 1,100 to 1,300 PT-modified d(G PS A) motifs per genome, with 6m A arising from a yet-to-be-identified methyltransferase. To further explore PT and 6m A in another consensus sequence, G PS 6m ATC, we engineered a strain of E. coli HST04 to express Dnd genes from Hahella chejuensis KCTC2396 (PT in G PS ATC) and Dam methyltransferase from E. coli DH10B ( 6m A in G 6m ATC). Based on this model, in vitro studies revealed reduced Dam activity in G PS ATC-containing oligonucleotides whereas single-molecule real-time sequencing of HST04 DNA revealed 6m A in all 2,058 G PS ATC sites (5% of 37,698 total GATC sites). This model system also revealed temperature-sensitive restriction by DndFGH in KCTC2396 and B7A, which was exploited to discover that 6m A can substitute for PT to confer resistance to restriction by the DndFGH system. These results point to complex but unappreciated interactions between DNA modification systems and raise the possibility of coevolution of interacting systems to facilitate the function of each.T he emergence of convergent technologies has led to a growing appreciation for the diversity of DNA modifications in microbial epigenetics and restriction-modification (R-M) systems (1-3). DNA methylation, the most extensively studied genetic modification, was originally discovered in bacteria in the context of R-M systems involving a methyltransferase (MTase) that modifies "self" DNA at specific target sites and a cognate restriction endonuclease (REase) that discriminates and destroys unmodified invading DNA (3-5). R-M systems are ubiquitous in prokaryotes and are classified into four types (I, II, III, and IV) based on their molecular structure, sequence recognition, cleavage position, and cofactor requirements (3, 6, 7). However, some MTases exist alone, without an apparent cognate REase partner. These so-called "orphan" MTases include DNA adenine methylase (Dam), which modifies the adenine N-6 in the GATC motif, DNA cytosine methylase (Dcm), which methylates C-5 of the second cytosine in CC(A/T) GG sequences, and cell cycle-regulated methylase (CcrM), which methylates the N-6 of adenine in GANTC (N = A, T, C, or G) (8). Despite the absence of cognate REases, orphan MTases still confer immunity against the virulence of a parasitic R-M complex with the same target sites (9). In addition to defense against bacteriophages and transposons, DNA m...

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Roles of DNA Adenine Methylation in Regulating Bacterial Gene Expression and Virulence

Cited by 302 publications

References 95 publications

Cell Elongation and Cell Death of Helicobacter pylori Is Modulated by the Disruption of cdrA (Cell Division‐Related Gene A)

Cell Elongation and Cell Death of Helicobacter pylori Is Modulated by the Disruption of cdrA (Cell Division‐Related Gene A)

Diverse Functions of Restriction-Modification Systems in Addition to Cellular Defense

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

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