scholarly journals DNA sequence repeats identify numerous Type I restriction‐modification systems that are potential epigenetic regulators controlling phase‐variable regulons; phasevarions

2019 ◽  
Vol 34 (1) ◽  
pp. 1038-1051 ◽  
Author(s):  
John M. Atack ◽  
Chengying Guo ◽  
Long Yang ◽  
Yaoqi Zhou ◽  
Michael P. Jennings
Keyword(s):  
Dna Sequence ◽  
Type I ◽  
Phase Variable ◽  
Numerous Type ◽  
Epigenetic Regulators ◽  
Dna Sequence Repeats ◽  
Restriction Modification ◽  
Restriction Modification Systems

scholarly journals Phase-variable methylation and epigenetic regulation by type I restriction–modification systems

2017 ◽  
Vol 41 (Supp_1) ◽  
pp. S3-S15 ◽  
Author(s):  
Megan De Ste Croix ◽  
Irene Vacca ◽  
Min Jung Kwun ◽  
Joseph D. Ralph ◽  
Stephen D. Bentley ◽  
...  
Keyword(s):  
Epigenetic Regulation ◽  
Type I ◽  
Phase Variable ◽  
Restriction Modification ◽  
Restriction Modification Systems

Epigenetic Regulation of Virulence and Immunoevasion by Phase-Variable Restriction-Modification Systems in Bacterial Pathogens

2020 ◽  
Vol 74 (1) ◽  
pp. 655-671
Author(s):  
Kate L. Seib ◽  
Yogitha N. Srikhanta ◽  
John M. Atack ◽  
Michael P. Jennings
Keyword(s):  
Bacterial Pathogens ◽  
Phase Variation ◽  
Global Changes ◽  
Type I ◽  
Phase Variable ◽  
Human Pathogens ◽  
Variable Expression ◽  
Host Immune Responses ◽  
Restriction Modification ◽  
Restriction Modification Systems

Human-adapted bacterial pathogens use a mechanism called phase variation to randomly switch the expression of individual genes to generate a phenotypically diverse population to adapt to challenges within and between human hosts. There are increasing reports of restriction-modification systems that exhibit phase-variable expression. The outcome of phase variation of these systems is global changes in DNA methylation. Analysis of phase-variable Type I and Type III restriction-modification systems in multiple human-adapted bacterial pathogens has demonstrated that global changes in methylation regulate the expression of multiple genes. These systems are called phasevarions (phase-variable regulons). Phasevarion switching alters virulence phenotypes and facilitates evasion of host immune responses. This review describes the characteristics of phasevarions and implications for pathogenesis and immune evasion. We present and discuss examples of phasevarion systems in the major human pathogens Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, Helicobacter pylori, Moraxella catarrhalis, and Streptococcus pneumoniae.

scholarly journals Phasevarions of bacterial pathogens – phase-variable epigenetic regulators evolving from restriction–modification systems

Microbiology ◽  
2019 ◽  
Vol 165 (9) ◽  
pp. 917-928 ◽  
Author(s):  
Zachary N. Phillips ◽  
Asma-Ul Husna ◽  
Michael P. Jennings ◽  
Kate L. Seib ◽  
John M. Atack
Keyword(s):  
Bacterial Pathogens ◽  
Phase Variable ◽  
Epigenetic Regulators ◽  
Restriction Modification ◽  
Restriction Modification Systems

scholarly journals Genetic variation regulates the activation and specificity of Restriction-Modification systems in Neisseria gonorrhoeae

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Leonor Sánchez-Busó ◽  
Daniel Golparian ◽  
Julian Parkhill ◽  
Magnus Unemo ◽  
Simon R. Harris
Keyword(s):  
Neisseria Gonorrhoeae ◽  
Single Molecule ◽  
Regulation Of Gene Expression ◽  
Phase Variation ◽  
Type I ◽  
Dam Methylase ◽  
Different Strains ◽  
Methylation Patterns ◽  
Restriction Modification ◽  
Restriction Modification Systems

Abstract Restriction-Modification systems (RMS) are one of the main mechanisms of defence against foreign DNA invasion and can have an important role in the regulation of gene expression. The obligate human pathogen Neisseria gonorrhoeae carries one of the highest loads of RMS in its genome; between 13 to 15 of the three main types. Previous work has described their organization in the reference genome FA1090 and has inferred the associated methylated motifs. Here, we studied the structure of RMS and target methylated motifs in 25 gonococcal strains sequenced with Single Molecule Real-Time (SMRT) technology, which provides data on DNA modification. The results showed a variable picture of active RMS in different strains, with phase variation switching the activity of Type III RMS, and both the activity and specificity of a Type I RMS. Interestingly, the Dam methylase was found in place of the NgoAXI endonuclease in two of the strains, despite being previously thought to be absent in the gonococcus. We also identified the real methylation target of NgoAXII as 5′-GCAGA-3′, different from that previously described. Results from this work give further insights into the diversity and dynamics of RMS and methylation patterns in N. gonorrhoeae.

scholarly journals Phase-variable restriction/modification systems are required for Helicobacter pylori colonization

Gut Pathogens ◽  
2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Jonathan C Gauntlett ◽  
Hans-Olof Nilsson ◽  
Alma Fulurija ◽  
Barry J Marshall ◽  
Mohammed Benghezal
Keyword(s):  
Helicobacter Pylori ◽  
Phase Variable ◽  
Restriction Modification ◽  
Restriction Modification Systems

scholarly journals Systematic analysis of REBASE identifies numerous Type I restriction-modification systems that contain duplicated, variable hsdS specificity genes that randomly switch methyltransferase specificity by recombination

2020 ◽  
Author(s):  
John M. Atack ◽  
Chengying Guo ◽  
Thomas Litfin ◽  
Long Yang ◽  
Patrick J. Blackall ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Bacterial Species ◽  
Dna Methyltransferases ◽  
Inverted Repeats ◽  
Global Changes ◽  
Length Variation ◽  
Type I ◽  
Phase Variable ◽  
Global Methylation ◽  
Restriction Modification

AbstractN6-adenine DNA methyltransferases associated with some Type I and Type III restriction-modification (R-M) systems are able to randomly switch expression by variation in the length of locus-encoded simple sequence repeats (SSRs). SSR tract-length variation causes ON/OFF switching of methyltransferase expression, resulting in genome-wide methylation differences, and global changes in gene expression. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria. A distinct switching system has also been described in Type I R-M systems, based on recombination-driven changes in hsdS genes, which dictate the DNA target site. In order to determine the prevalence of recombination-driven phasevarions, we generated a program called RecombinationRepeatSearch to interrogate REBASE and identify the presence and number of inverted repeats of hsdS downstream of Type I R-M loci. We report that 5.9% of Type I R-M systems have duplicated variable hsdS genes containing inverted repeats capable of phase-variation. We report the presence of these systems in the major pathogens Enterococcus faecalis and Listeria monocytogenes, which will have important implications for pathogenesis and vaccine development. These data suggest that in addition to SSR-driven phasevarions, many bacteria have independently evolved phase-variable Type I R-M systems via recombination between multiple, variable hsdS genes.ImportanceMany bacterial species contain DNA methyltransferases that have random on/off switching of expression. These systems called phasevarions (phase-variable regulons) control the expression of multiple genes by global methylation changes. In every previously characterised phasevarion, genes involved in pathobiology, antibiotic resistance, and potential vaccine candidates are randomly varied in their expression, commensurate with methyltransferase switching. A systematic study to determine the extent of phasevarions controlled by invertible Type I R-M systems has never before been performed. Understanding how bacteria regulate genes is key to the study of physiology, virulence, and vaccine development; therefore it is critical to identify and characterize phase-variable methyltransferases controlling phasevarions.

scholarly journals Methylation by multiple type I restriction modification systems avoids influencing gene regulation in uropathogenic Escherichia coli

2021 ◽  
Author(s):  
Kurosh S Mehershahi ◽  
Swaine Chen
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Dna Methylation ◽  
Gene Regulation ◽  
Detectable Effect ◽  
Epigenetic Mark ◽  
Type I ◽  
E Coli ◽  
Restriction Modification ◽  
Restriction Modification Systems

DNA methylation is a common epigenetic mark that influences transcriptional regulation, and therefore cellular phenotype, across all domains of life, extending also to bacterial virulence. Both orphan methyltransferases and those from restriction modification systems (RMSs) have been co-opted to regulate virulence epigenetically in many bacteria. However, the potential regulatory role of DNA methylation mediated by archetypal Type I systems in Escherichia coli has never been studied. We demonstrated that removal of DNA methylated mediated by three different Escherichia coli Type I RMSs in three distinct E. coli strains had no detectable effect on gene expression or growth in a screen of 1190 conditions. Additionally, deletion of the Type I RMS EcoUTI in UTI89, a prototypical cystitis strain of E. coli , which led to loss of methylation at >750 sites across the genome, had no detectable effect on virulence in a murine model of ascending urinary tract infection (UTI). Finally, introduction of two heterologous Type I RMSs into UTI89 also resulted in no detectable change in gene expression or growth phenotypes. These results stand in sharp contrast with many reports of RMSs regulating gene expression in other bacteria, leading us to propose the concept of “regulation avoidance” for these E. coli Type I RMSs. We hypothesize that regulation avoidance is a consequence of evolutionary adaptation of both the RMSs and the E. coli genome. Our results provide a clear and (currently) rare example of regulation avoidance for Type I RMSs in multiple strains of E. coli , further study of which may provide deeper insights into the evolution of gene regulation and horizontal gene transfer.

scholarly journals Systematic Analysis of REBASE Identifies Numerous Type I Restriction-Modification Systems with Duplicated, Distinct hsdS Specificity Genes That Can Switch System Specificity by Recombination

mSystems ◽  
2020 ◽  
Vol 5 (4) ◽  
Author(s):  
John M. Atack ◽  
Chengying Guo ◽  
Thomas Litfin ◽  
Long Yang ◽  
Patrick J. Blackall ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Phase Variation ◽  
Dna Methyltransferases ◽  
Inverted Repeats ◽  
Global Changes ◽  
Type I ◽  
Phase Variable ◽  
Global Methylation ◽  
Content Type ◽  
Restriction Modification

ABSTRACT N6-Adenine DNA methyltransferases associated with some Type I and Type III restriction-modification (R-M) systems are able to undergo phase variation, randomly switching expression ON or OFF by varying the length of locus-encoded simple sequence repeats (SSRs). This variation of methyltransferase expression results in genome-wide methylation differences and global changes in gene expression. These epigenetic regulatory systems are called phasevarions, phase-variable regulons, and are widespread in bacteria. A distinct switching system has also been described in Type I R-M systems, based on recombination-driven changes in hsdS genes, which dictate the DNA target site. In order to determine the prevalence of recombination-driven phasevarions, we generated a program called RecombinationRepeatSearch to interrogate REBASE and identify the presence and number of inverted repeats of hsdS downstream of Type I R-M loci. We report that 3.9% of Type I R-M systems have duplicated variable hsdS genes containing inverted repeats capable of phase variation. We report the presence of these systems in the major pathogens Enterococcus faecalis and Listeria monocytogenes, which could have important implications for pathogenesis and vaccine development. These data suggest that in addition to SSR-driven phasevarions, many bacteria have independently evolved phase-variable Type I R-M systems via recombination between multiple, variable hsdS genes. IMPORTANCE Many bacterial species contain DNA methyltransferases that have random on/off switching of expression. These systems, called phasevarions (phase-variable regulons), control the expression of multiple genes by global methylation changes. In every previously characterized phasevarion, genes involved in pathobiology, antibiotic resistance, and potential vaccine candidates are randomly varied in their expression, commensurate with methyltransferase switching. Our systematic study to determine the extent of phasevarions controlled by invertible Type I R-M systems will provide valuable information for understanding how bacteria regulate genes and is key to the study of physiology, virulence, and vaccine development; therefore, it is critical to identify and characterize phase-variable methyltransferases controlling phasevarions.

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