scholarly journals Prevalence of phase variable epigenetic invertons among host-associated bacteria

2020 ◽  
Vol 48 (20) ◽  
pp. 11468-11485
Author(s):  
Xueting Huang ◽  
Juanjuan Wang ◽  
Jing Li ◽  
Yanni Liu ◽  
Xue Liu ◽  
...  
Keyword(s):  
Type I ◽  
Phase Variable ◽  
Bacterial Host ◽  
Dna Endonuclease ◽  
Associated Bacteria ◽  
Bacterial Phyla ◽  
Cellular Physiology ◽  
Allelic Variations ◽  
Restriction Modification

Abstract Type I restriction-modification (R-M) systems consist of a DNA endonuclease (HsdR, HsdM and HsdS subunits) and methyltransferase (HsdM and HsdS subunits). The hsdS sequences flanked by inverted repeats (referred to as epigenetic invertons) in certain Type I R-M systems undergo invertase-catalyzed inversions. Previous studies in Streptococcus pneumoniae have shown that hsdS inversions within clonal populations produce subpopulations with profound differences in the methylome, cellular physiology and virulence. In this study, we bioinformatically identified six major clades of the tyrosine and serine family invertases homologs from 16 bacterial phyla, which potentially catalyze hsdS inversions in the epigenetic invertons. In particular, the epigenetic invertons are highly enriched in host-associated bacteria. We further verified hsdS inversions in the Type I R-M systems of four representative host-associated bacteria and found that each of the resultant hsdS allelic variants specifies methylation of a unique DNA sequence. In addition, transcriptome analysis revealed that hsdS allelic variations in Enterococcus faecalis exert significant impact on gene expression. These findings indicate that epigenetic switches driven by invertases in the epigenetic invertons broadly operate in the host-associated bacteria, which may broadly contribute to bacterial host adaptation and virulence beyond the role of the Type I R-M systems against phage infection.

scholarly journals Roles of Diffusible Signals in Communication Among Plant-Associated Bacteria

2007 ◽  
Vol 97 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Leland S. Pierson ◽  
Elizabeth A. Pierson
Keyword(s):  
Gene Expression ◽  
Control Gene ◽  
Bacterial Host ◽  
Diverse Range ◽  
Associated Bacteria ◽  
Host Interactions ◽  
Control Gene Expression ◽  
Pseudomonas Species ◽  
Interkingdom Communication

In nature, Pseudomonas species compete and co-exist in mixed communities with a diversity of prokaryotic and eukaryotic micro- and macroorganisms. Many bacteria produce various signals that control gene expression and thus contribute to specific bacterial behaviors and coordinate essential functions with other members of the community. The best-studied signaling compounds are N-acyl-homoserine lactones (AHLs), which are involved in quorum sensing (QS) regulation and are produced by a diverse range of bacterial taxa. To date, research on QS has focused on how signals control gene expression in the bacterial cell and the role of these signals in positive and negative communication among different groups of organisms. Additionally, mechanisms for AHL decay and AHL utilization as sole carbon/energy sources have been identified. Some host organisms produce compounds that can mimic AHLs, and some bacterial signals can influence host gene expression. Thus, interkingdom communication may be more widespread than previously believed. Our current understanding of individual, community and bacterial-host interactions is still in its infancy and there are many exciting discoveries yet to be made.

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 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.

scholarly journals Analysis of a phase-variable restriction modification system of the human gut symbiont Bacteroides fragilis

2020 ◽  
Vol 48 (19) ◽  
pp. 11040-11053
Author(s):  
Nadav Ben-Assa ◽  
Michael J Coyne ◽  
Alexey Fomenkov ◽  
Jonathan Livny ◽  
William P Robins ◽  
...  
Keyword(s):  
Bacteroides Fragilis ◽  
Surface Proteins ◽  
Type I ◽  
Phase Variable ◽  
Modification System ◽  
Restriction Modification System ◽  
Recognition Sites ◽  
Specificity Protein ◽  
Restriction Modification

Abstract The genomes of gut Bacteroidales contain numerous invertible regions, many of which contain promoters that dictate phase-variable synthesis of surface molecules such as polysaccharides, fimbriae, and outer surface proteins. Here, we characterize a different type of phase-variable system of Bacteroides fragilis, a Type I restriction modification system (R-M). We show that reversible DNA inversions within this R-M locus leads to the generation of eight specificity proteins with distinct recognition sites. In vitro grown bacteria have a different proportion of specificity gene combinations at the expression locus than bacteria isolated from the mammalian gut. By creating mutants, each able to produce only one specificity protein from this region, we identified the R-M recognition sites of four of these S-proteins using SMRT sequencing. Transcriptome analysis revealed that the locked specificity mutants, whether grown in vitro or isolated from the mammalian gut, have distinct transcriptional profiles, likely creating different phenotypes, one of which was confirmed. Genomic analyses of diverse strains of Bacteroidetes from both host-associated and environmental sources reveal the ubiquity of phase-variable R-M systems in this phylum.

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

scholarly journals Methylation Warfare: Interaction of Pneumococcal Bacteriophages with Their Host

2019 ◽  
Vol 201 (19) ◽  
Author(s):  
Leonardo Furi ◽  
Liam A. Crawford ◽  
Guillermo Rangel-Pineros ◽  
Ana S. Manso ◽  
Megan De Ste Croix ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lytic Replication ◽  
Host Cells ◽  
Transcriptional Analysis ◽  
Type I ◽  
Phase Variable ◽  
Abortive Infection ◽  
Content Type ◽  
Variable Type ◽  
Restriction Modification

ABSTRACTVirus-host interactions are regulated by complex coevolutionary dynamics. InStreptococcus pneumoniae, phase-variable type I restriction-modification (R-M) systems are part of the core genome. We hypothesized that the ability of the R-M systems to switch between six target DNA specificities also has a key role in preventing the spread of bacteriophages. Using the streptococcal temperate bacteriophage SpSL1, we show that the variants of both the SpnIII and SpnIV R-M systems are able to restrict invading bacteriophage with an efficiency approximately proportional to the number of target sites in the bacteriophage genome. In addition to restriction of lytic replication, SpnIII also led to abortive infection in the majority of host cells. During lytic infection, transcriptional analysis found evidence of phage-host interaction through the strong upregulation of thenrdRnucleotide biosynthesis regulon. During lysogeny, the phage had less of an effect on host gene regulation. This research demonstrates a novel combined bacteriophage restriction and abortive infection mechanism, highlighting the importance that the phase-variable type I R-M systems have in the multifunctional defense against bacteriophage infection in the respiratory pathogenS. pneumoniae.IMPORTANCEWith antimicrobial drug resistance becoming an increasing burden on human health, much attention has been focused on the potential use of bacteriophages and their enzymes as therapeutics. However, the investigations into the physiology of the complex interactions of bacteriophages with their hosts have attracted far less attention, in comparison. This work describes the molecular characterization of the infectious cycle of a bacteriophage in the important human pathogenStreptococcus pneumoniaeand explores the intricate relationship between phase-variable host defense mechanisms and the virus. This is the first report showing how a phase-variable type I restriction-modification system is involved in bacteriophage restriction while it also provides an additional level of infection control through abortive infection.

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 A Type I Restriction Modification System Influences Genomic Evolution Driven by Horizontal Gene Transfer in Paenibacillus polymyxa

2021 ◽  
Vol 12 ◽  
Author(s):  
Ziyan Chen ◽  
Minjia Shen ◽  
Chengyao Mao ◽  
Chenyu Wang ◽  
Panhong Yuan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Animal Husbandry ◽  
Paenibacillus Polymyxa ◽  
Genomic Islands ◽  
Type I ◽  
Genomic Evolution ◽  
Modification System ◽  
Restriction Modification System ◽  
Restriction Modification

Considered a “Generally Recognized As Safe” (GRAS) bacterium, the plant growth–promoting rhizobacterium Paenibacillus polymyxa has been widely applied in agriculture and animal husbandry. It also produces valuable compounds that are used in medicine and industry. Our previous work showed the presence of restriction modification (RM) system in P. polymyxa ATCC 842. Here, we further analyzed its genome and methylome by using SMRT sequencing, which revealed the presence of a larger number of genes, as well as a plasmid documented as a genomic region in a previous report. A number of mobile genetic elements (MGEs), including 78 insertion sequences, six genomic islands, and six prophages, were identified in the genome. A putative lysozyme-encoding gene from prophage P6 was shown to express lysin which caused cell lysis. Analysis of the methylome and genome uncovered a pair of reverse-complementary DNA methylation motifs which were widespread in the genome, as well as genes potentially encoding their cognate type I restriction-modification system PpoAI. Further genetic analysis confirmed the function of PpoAI as a RM system in modifying and restricting DNA. The average frequency of the DNA methylation motifs in MGEs was lower than that in the genome, implicating a role of PpoAI in restricting MGEs during genomic evolution of P. polymyxa. Finally, comparative analysis of R, M, and S subunits of PpoAI showed that homologs of the PpoAI system were widely distributed in species belonging to other classes of Firmicute, implicating a role of the ancestor of PpoAI in the genomic evolution of species beyond Paenibacillus.

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