Novel Identification of Bacterial Epigenetic Regulations Would Benefit From a Better Exploitation of Methylomic Data

DNA methylation can be part of epigenetic mechanisms, leading to cellular subpopulations with heterogeneous phenotypes. While prokaryotic phenotypic heterogeneity is of critical importance for a successful infection by several major pathogens, the exact mechanisms involved in this phenomenon remain unknown in many cases. Powerful sequencing tools have been developed to allow the detection of the DNA methylated bases at the genome level, and they have recently been extensively applied on numerous bacterial species. Some of these tools are increasingly used for metagenomics analysis but only a limited amount of the available methylomic data is currently being exploited. Because newly developed tools now allow the detection of subpopulations differing in their genome methylation patterns, it is time to emphasize future strategies based on a more extensive use of methylomic data. This will ultimately help to discover new epigenetic gene regulations involved in bacterial phenotypic heterogeneity, including during host-pathogen interactions.

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A Genomic Distance Based on MUM Indicates Discontinuity between Most Bacterial Species and Genera

Journal of Bacteriology ◽

10.1128/jb.01202-08 ◽

2008 ◽

Vol 191 (1) ◽

pp. 91-99 ◽

Cited By ~ 115

Author(s):

Marc Deloger ◽

Meriem El Karoui ◽

Marie-Agnès Petit

Keyword(s):

Dna Sequences ◽

Dna Content ◽

Core Genome ◽

Biological Diversity ◽

Bacterial Species ◽

Genomic Distance ◽

The Core ◽

Intraspecies Diversity ◽

Genome Level ◽

Definition Of

ABSTRACT The fundamental unit of biological diversity is the species. However, a remarkable extent of intraspecies diversity in bacteria was discovered by genome sequencing, and it reveals the need to develop clear criteria to group strains within a species. Two main types of analyses used to quantify intraspecies variation at the genome level are the average nucleotide identity (ANI), which detects the DNA conservation of the core genome, and the DNA content, which calculates the proportion of DNA shared by two genomes. Both estimates are based on BLAST alignments for the definition of DNA sequences common to the genome pair. Interestingly, however, results using these methods on intraspecies pairs are not well correlated. This prompted us to develop a genomic-distance index taking into account both criteria of diversity, which are based on DNA maximal unique matches (MUM) shared by two genomes. The values, called MUMi, for MUM index, correlate better with the ANI than with the DNA content. Moreover, the MUMi groups strains in a way that is congruent with routinely used multilocus sequence-typing trees, as well as with ANI-based trees. We used the MUMi to determine the relatedness of all available genome pairs at the species and genus levels. Our analysis reveals a certain consistency in the current notion of bacterial species, in that the bulk of intraspecies and intragenus values are clearly separable. It also confirms that some species are much more diverse than most. As the MUMi is fast to calculate, it offers the possibility of measuring genome distances on the whole database of available genomes.

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Importance of Genetic Factors in Male Fertility Disorders, Clinical Relevance of Epigenetic Markers in Male Infertility

Revista de Chimie ◽

10.37358/rc.19.7.7381 ◽

2019 ◽

Vol 70 (7) ◽

pp. 2566-2570

Author(s):

Dragos Botezatu ◽

Cristina Popescu ◽

Andrei-Dan Korodi ◽

Cristian Furau ◽

Gheorghe Furau ◽

...

Keyword(s):

Dna Methylation ◽

Male Infertility ◽

Male Fertility ◽

Complex Problem ◽

The Body ◽

Control Group ◽

Global Methylation ◽

Methylation Of Dna ◽

Genome Methylation ◽

Methylation Patterns

Male infertility is a common and complex problem affecting 1 out of 20 men. Despite extensive research in this area, in many cases, the underlying causes are unknown. Epigenetic changes control a series of processes within the body, including male fertility. Classification of infertile men using a more detailed analysis of DNA methylation patterns could reveal a new level of low rates of fertilization, implantation, or pregnancy. In this context, it seemed to us to use the techniques available to evaluate the degree of global methylation of DNA in infertile patients who have modified sperm counts, but also those who apparently do not have a clear cause of infertility. For this we used the Quest 5mC-Zymoresaerch-ELISA kit that can detect within about 5 hours the global level of genome methylation. Claims on which common illnesses have an epigenetic base are still open to speculation, but if true, it can imprint a new direction in medicine. Our data, although from a pilot study, are consistent with those in the literature. A recent study has shown that DNA methylation levels were significantly higher in oligoasthenoteratozoospermia patients than in the control group and the increase in global DNA methylation and histone retention in men with oligoasthenoteratozoospermia.

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Genome methylation patterns across castes and generations in a parasitoid wasp

Ecology and Evolution ◽

10.1002/ece3.2395 ◽

2016 ◽

Vol 6 (22) ◽

pp. 7943-7953 ◽

Cited By ~ 6

Author(s):

Roei Shaham ◽

Rachel Ben-Shlomo ◽

Uzi Motro ◽

Tamar Keasar

Keyword(s):

Parasitoid Wasp ◽

Genome Methylation ◽

Methylation Patterns

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Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1912129116 ◽

2019 ◽

Vol 116 (48) ◽

pp. 24285-24295 ◽

Cited By ~ 16

Author(s):

Iradj Sobhani ◽

Emma Bergsten ◽

Séverine Couffin ◽

Aurélien Amiot ◽

Biba Nebbad ◽

...

Keyword(s):

Colorectal Cancer ◽

Bacterial Species ◽

Aberrant Crypt Foci ◽

Sporadic Colorectal Cancer ◽

Gene Promoters ◽

Normal Tissues ◽

Complex Interactions ◽

Dna Alterations ◽

Methylation Patterns ◽

Epigenetic Signatures

Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls’ microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.

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Oocyte IVM or vitrification significantly impairs DNA methylation patterns in blastocysts as analysed by single-cell whole-genome methylation sequencing

Reproduction Fertility and Development ◽

10.1071/rd19234 ◽

2020 ◽

Vol 32 (7) ◽

pp. 676

Author(s):

Ya-Han Zhao ◽

Jing-Jing Wang ◽

Pei-Pei Zhang ◽

Hai-Sheng Hao ◽

Yun-Wei Pang ◽

...

Keyword(s):

Single Cell ◽

Protein Phosphatase ◽

Poor Quality ◽

Protein Phosphatase 1 ◽

Regulatory Subunit ◽

Whole Genome ◽

Genome Methylation ◽

Sequencing Technique ◽

Methylation Patterns

To explore the mechanisms leading to the poor quality of IVF blastocysts, the single-cell whole-genome methylation sequencing technique was used in this study to analyse the methylation patterns of bovine blastocysts derived from invivo, fresh (IVF) or vitrified (V_IVF) oocytes. Genome methylation levels of blastocysts in the IVF and V_IVF groups were significantly lower than those of the invivo group (P<0.05). In all, 1149 differentially methylated regions (DMRs) were identified between the IVF and invivo groups, 1578 DMRs were identified between the V_IVF and invivo groups and 151 DMRs were identified between the V_IVF and IVF groups. For imprinted genes, methylation levels of insulin-like growth factor 2 receptor (IGF2R) and protein phosphatase 1 regulatory subunit 9A (PPP1R9A) were lower in the IVF and V_IVF groups than in the invivo group, and the methylation level of paternally expressed 3 (PEG3) was lower in the V_IVF group than in the IVF and invivo groups. Genes with DMRs between the IVF and invivo and the V_IVF and IVF groups were primarily enriched in oocyte maturation pathways, whereas DMRs between the V_IVF and invivo groups were enriched in fertilisation and vitrification-vulnerable pathways. The results of this study indicate that differences in the methylation of critical DMRs may contribute to the differences in quality between invitro- and invivo-derived embryos.

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MITEAba12, a Novel Mobile Miniature Inverted-Repeat Transposable Element Identified inAcinetobacter baumanniiATCC 17978 and Its Prevalence across theMoraxellaceaeFamily

mSphere ◽

10.1128/mspheredirect.00028-19 ◽

2019 ◽

Vol 4 (1) ◽

Author(s):

Felise G. Adams ◽

Melissa H. Brown

Keyword(s):

Inverted Repeat ◽

Bacterial Species ◽

Consensus Sequence ◽

Target Site ◽

The Novel ◽

Bacterial Genomes ◽

Content Type ◽

Promoter Sequences ◽

Moraxella Osloensis ◽

Genome Level

ABSTRACTInsertion sequences (IS) are fundamental mediators of genome plasticity with the potential to generate phenotypic variation with significant evolutionary outcomes. Here, a recently active miniature inverted-repeat transposon element (MITE) was identified in a derivative ofAcinetobacter baumanniiATCC 17978 after being subjected to stress conditions. Transposition of the novel element led to the disruption of thehnsgene, resulting in a characteristic hypermotile phenotype. DNA identity shared between the terminal inverted repeats of this MITE and coresident ISAba12elements, together with the generation of 9-bp target site duplications, provides strong evidence that ISAba12elements were responsible for mobilization of the MITE (designated MITEAba12) within this strain. A wider genome-level survey identified MITEAba12in 30 additionalAcinetobactergenomes at various frequencies and oneMoraxella osloensisgenome. Ninety MITEAba12copies could be identified, of which 40% had target site duplications, indicating recent transposition events. Elements ranged between 111 and 114 bp; 90% were 113 bp in length. Using the MITEAba12consensus sequence, putative outward-facingEscherichia coliσ70 promoter sequences in both orientations were identified. The identification of transcripts originating from the promoter in one direction supports the proposal that the element can influence neighboring host gene transcription. The location of MITEAba12varied significantly between and within genomes, preferentially integrating into AT-rich regions. Additionally, a copy of MITEAba12was identified in a novel 8.5-kb composite transposon, Tn6645, in theM. osloensisCCUG 350 chromosome. Overall, this study shows that MITEAba12is the most abundant nonautonomous element currently found inAcinetobacter.IMPORTANCEOne of the most important weapons in the armory ofAcinetobacteris its impressive genetic plasticity, facilitating rapid genetic mutations and rearrangements as well as integration of foreign determinants carried by mobile genetic elements. Of these, IS are considered one of the key forces shaping bacterial genomes and ultimately evolution. We report the identification of a novel nonautonomous IS-derived element present in multiple bacterial species from theMoraxellaceaefamily and its recent translocation into thehnslocus in theA. baumanniiATCC 17978 genome. The latter finding adds new knowledge to only a limited number of documented examples of MITEs in the literature and underscores the plastic nature of thehnslocus inA. baumannii. MITEAba12, and its predicted parent(s), may be a source of substantial adaptive evolution within environmental and clinically relevant bacterial pathogens and, thus, have broad implications for niche-specific adaptation.

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Inoculation Period and Citrus Host Effect Establishment of New Infections of ‘Candidatus Liberibacter asiaticus’ Transmitted via Vegetative Grafting

Plant Disease ◽

10.1094/pdis-09-19-2022-re ◽

2020 ◽

Vol 104 (7) ◽

pp. 1894-1899

Author(s):

Mark E. Hilf ◽

Weiqi Luo

Keyword(s):

Survival Analysis ◽

Bacterial Species ◽

Systemic Infection ◽

Candidatus Liberibacter Asiaticus ◽

Susceptibility To Infection ◽

Successful Infection ◽

Significant Difference ◽

Candidatus Liberibacter ◽

Liberibacter Asiaticus ◽

Pathogen Dna

Vegetative grafting is a common method of transmitting and propagating ‘Candidatus Liberibacter asiaticus’, the bacterial species accepted as the causal agent of the citrus disease huanglongbing (HLB). Generally, infected tissue that is grafted to a receptor tree remains in place indefinitely to ensure transmission. In this study, individual HLB-symptomatic leaves were grafted as ‘Ca. L. asiaticus’ inoculum sources to receptor trees of six citrus types and removed after an inoculation period (IP) of 21, 51, or 81 days. The goal was to assess the effect of varying IPs on transmission of bacteria to the receptor tree and on the successful establishment of a new infection. Survival analysis of data from three trials showed a significantly reduced proportion of infected trees with an IP of 21 days compared with IPs of 51 and 81 days but that there was no significant difference in the proportion of infected trees between IPs of 51 and 81 days. In addition, the time to first detection of pathogen DNA in an infected tree was delayed significantly for the 21-day IP when compared with the 51- and 81-day IPs. Survival analysis showed that the probability of infection of sweet orange trees was significantly higher than for trees of five other citrus types throughout the experiment. There was no significant difference between the infection probabilities of these latter five citrus types. The data from this study show that successful infection by grafting is dependent upon the time of exposure to the inoculum, that shorter IPs increase the time needed to establish a systemic infection, and that citrus types vary in their overall susceptibility to infection by ‘Ca. L. asiaticus’.

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Gut Microbiota as an Epigenetic Regulator: Pilot Study Based on Whole-Genome Methylation Analysis

mBio ◽

10.1128/mbio.02113-14 ◽

2014 ◽

Vol 5 (6) ◽

Cited By ~ 81

Author(s):

Himanshu Kumar ◽

Riikka Lund ◽

Asta Laiho ◽

Krista Lundelin ◽

Ruth E. Ley ◽

...

Keyword(s):

Lipid Metabolism ◽

Gut Microbiota ◽

Pregnant Women ◽

Methylation Status ◽

Differential Methylation ◽

Gene Promoters ◽

Dominant Group ◽

Bacterial Phyla ◽

Genome Methylation ◽

Methylation Patterns

ABSTRACT The core human gut microbiota contributes to the developmental origin of diseases by modifying metabolic pathways. To evaluate the predominant microbiota as an epigenetic modifier, we classified 8 pregnant women into two groups based on their dominant microbiota, i.e., Bacteroidetes, Firmicutes, and Proteobacteria. Deep sequencing of DNA methylomes revealed a clear association between bacterial predominance and epigenetic profiles. The genes with differentially methylated promoters in the group in which Firmicutes was dominant were linked to risk of disease, predominantly to cardiovascular disease and specifically to lipid metabolism, obesity, and the inflammatory response. This is one of the first studies that highlights the association of the predominant bacterial phyla in the gut with methylation patterns. Further longitudinal and in-depth studies targeting individual microbial species or metabolites are recommended to give us a deeper insight into the molecular mechanism of such epigenetic modifications. IMPORTANCE Epigenetics encompasses genomic modifications that are due to environmental factors and do not affect the nucleotide sequence. The gut microbiota has an important role in human metabolism and could be a significant environmental factor affecting our epigenome. To investigate the association of gut microbiota with epigenetic changes, we assessed pregnant women and selected the participants based on their predominant gut microbiota for a study on their postpartum methylation profile. Intriguingly, we found that blood DNA methylation patterns were associated with gut microbiota profiles. The gut microbiota profiles, with either Firmicutes or Bacteroidetes as a dominant group, correlated with differential methylation status of gene promoters functionally associated with cardiovascular diseases. Furthermore, differential methylation of gene promoters linked to lipid metabolism and obesity was observed. For the first time, we report here a position of the predominant gut microbiota in epigenetic profiling, suggesting one potential mechanism in obesity with comorbidities, if proven in further in-depth studies.

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Large scale changes in host methylation patterns induced by IncA/C plasmid transformation inVibrio cholerae

10.1101/399964 ◽

2018 ◽

Author(s):

Ruibai Wang ◽

Kanglin Wan

Keyword(s):

Drug Resistance ◽

Host Range ◽

Vibrio Cholerae ◽

Horizontal Transfer ◽

Large Scale ◽

Epigenetic Modification ◽

Bacterial Species ◽

Multi Drug Resistance ◽

Broad Host Range ◽

Methylation Patterns

AbstractDNA methylation is a central epigenetic modification and has diverse biological functions in eukaryotic and prokaryotic organisms alike. The IncA/C plasmid genomes are approximately 150kb in length and harbour three methylase genes, two of which demonstrate cytosine specificity. Transformation of theVibrio choleraestrain C6706 with the IncA/C plasmid pVC211 resulted in a significant relabelling of the methylation patterns on the host chromosomes. The new methylation patterns induced by transformation with IncA/C plasmid were accepted by the restriction enzymes of the host’s restriction modification (RM) system. These data uncover a novel mechanism by which plasmids can be compatible with a host’s RM system and suggest a possible reason that plasmids of the IncA/C family are broad-host-range.Author summaryAntibiotic resistance of bacteria is a growing serious problem worldwidely and the horizontal transfer of multi-drug resistance genes mediated by plasmids within and between species of bacteria is the main reason. In the researches of multi-drug resistance ofVibrio cholerae, I have isolated several IncA/C plasmids. What impressed me most is their ability to accumulate the resistant genes. Moreover, they can transfer with high frequency and are stable in several bacterial species. There are at least three Tra regions on the IncA/C plasmid which containing components of the Type 4 Secretion System and are important for conjugative transfer of plasmids. So the horizontal transfer ability of IncA/C plasmids is reasonable. There are three methylase genes on the small genome of IncA/C plasmids, which demonstrate cytosine specificity and are seldom in bacteria. Their modification target and roles are interesting. Here, we analysed the methylation profiles of the hostV. choeraeinduced by the plasmid pVC211 and found that they were completely changed. In addition to replicons, this may be a novel mechanism that plasmid cross the barrier of the host’s RM system and become broad-host range. Changing the activity of methylase in IncA/C plasmids may be a new way to affect the stability of IncA/C plasmids to eliminate these multidrug-resistant plasmids from bacteria.

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A maternal effect regulates global DNA methylation patterns

10.1101/2020.08.15.252239 ◽

2020 ◽

Author(s):

Remco Loos ◽

Valeria Carola ◽

Enrica Audero ◽

Elena Brini ◽

Luisa Lo Iacono ◽

...

Keyword(s):

Dna Methylation ◽

Maternal Effect ◽

Cpg Island ◽

Inbred Mouse ◽

Mouse Strains ◽

Global Dna Methylation ◽

Global Methylation ◽

Genome Methylation ◽

Genetic And Environmental Factors ◽

Methylation Patterns

AbstractVariation in DNA methylation between individuals has been shown to be influenced by both genetic and environmental factors. However, the relative impact of genetic and non-genetic factors on DNA methylation patterns across the mammalian genome has not been systematically studied. We performed whole-genome methylation analysis in two inbred mouse strains, revealing striking differences in the global distribution of DNA methylation. Although global methylation patterns were indistinguishable for most genomic features, a significant increase in the number of unmethylated CpG-island promoters and first exons was observed between strains. Experiments using F1 reciprocal hybrid strains demonstrated that the genotype of the mother dictated global DNA methylation patterns. Cross-fostering experiments ruled out a postnatal maternal effect on these differences and suggested that they were driven by a prenatal maternal effect, possibly via differential deposition of maternal gene products into the oocyte or uterine environment. These data demonstrate that maternal effects have a major impact on global DNA methylation patterns.

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