A role for the bacterial GATC methylome in antibiotic stress survival

Cohen, Nadia; Roß, Christian; Jain, Saloni R.; Shapiro, Rebecca; Gutierrez, Arnaud; Belenky, Peter; Li, Hu; Collins, James J.

doi:10.1038/ng.3530

Cited by 95 publications

(105 citation statements)

References 75 publications

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“…Previous work focusing on both logarithmic phase growth and early stationary phase (no more than 24 h) has shown that GATC sites in the gammaproteobacteria are methylated by Dam to near completion (26–28). To date, there has yet to be a characterization of methylation levels through late stationary phase, through death phase, and into long-term stationary phase.…”

Section: Resultsmentioning

confidence: 99%

“…1C). Many of the sites identified are located within genes that encode proteins involved in transport or transcriptional regulation or are located in the inner membrane (Table 1), and several of these sites were recently identified as being hypomethylated (28). Greater than 20% (14/66) of the sites are located within genes known to be regulated by CRP-cyclic AMP (cAMP) which binds a consensus sequence that contains GATC.…”

Section: Resultsmentioning

confidence: 99%

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Genomewide Dam Methylation in Escherichia coli during Long-Term Stationary Phase

et al. 2016

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While it has been shown that methylation remains relatively constant into early stationary phase of E. coli, this study goes further through death phase and long-term stationary phase, a unique time in the bacterial life cycle due to nutrient limitation and strong selection for mutants with increased fitness. The absence of methylation at GATC sites can influence the mutation frequency within a population due to aberrant mismatch repair. Therefore, it is important to investigate the methylation status of GATC sites in an environment where cells may not prioritize methylation of the chromosome. This study demonstrates that chromosome methylation remains a priority even under conditions of nutrient limitation, indicating that continuous methylation at GATC sites could be under positive selection.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Genomewide Dam Methylation in Escherichia coli during Long-Term Stationary Phase

et al. 2016

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“…In addition, biological nanopores are able to discriminate not only the genome but also single base modifications such as 5-methylation of cytosine (5mC for DNA and m5C for RNA) and 6-methylation of adenine (6mA for DNA and 5mC for RNA) in native DNA/RNA[32]. Increasing evidence in last years suggests that DNA/RNA methylation can influence biological function, including regulation of DNA/RNA replication and repair, and gene expression[33–36]. Recently, Oliveira et al reported that DNA methyltransterase in Clostridioides difficile has able to mediate sporulation, C. difficile disease transmission and pathogenesis[37].…”

Section: Introductionmentioning

confidence: 99%

Profiling of Human Gut Virome with Oxford Nanopore Technology

Cao

Zhang

Dai

et al. 2020

Preprint

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AbstractHuman gut virome play critical roles in maintaining gut microbial composition and functionality, as well as host physiology and immunology. Yet, there are insufficient amount of studies on this topic mainly due to methodological limitations, including enrichment of viruses (phages and host viruses) as well as short read-length from current sequencing technology. Here we developed a full working protocol for analyzing human gut virome using physical enrichment, reverse transcription and random amplification, and eventually the state-of-art single-molecule real-time sequencing (SMRT) platform of Oxford Nanopore Technology (ONT). We demonstrate that sequencing viral DNA directly, or viral DNA/cDNA after amplification using ONT achieves much longer reads and provides more information regarding virome diversity, many of the virome sequences do not have match in current databases. Moreover, direct DNA sequencing of virome provides first insights into the epigenetic modifications on phages, where signals of methylations can be directly detected. Our study demonstrates that progressing sequencing technology and bioinformatic improvements will bring more knowledge into virome composition, diversity and potentially their important functions.HighlightsVirus-like particles were enriched from human stool samples;Viral nucleotides were sequenced with Oxford Nanopore Technology with and without amplification;Gut virome in humans showed highly individualized composition;Novel sequences and contigs were found to be the majority in the resulted sequences;Epigenetic modifications were detected directly on virus genomes.

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“…Methylation plays important roles in epigenetic gene regulation in both eukaryotic and prokaryotic organisms. Compared with the explicit function of Dam methylation in mismatch repair, initiation of chromosome replication, transcription regulation at promoters containing GATC sequences, gene expression, pathogenicity and DNA stable under antibiotic pressure [19], there are limited details known regarding the function of the Dcm MTase [2]. The discovery of two of the three MTase genes on the IncA/C 2 plasmid were cytosine-specific was intriguing.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Wan

2018

Preprint

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19DNA methylation is a central epigenetic modification and has diverse biological 20 functions in eukaryotic and prokaryotic organisms alike. The IncA/C plasmid 21 genomes are approximately 150kb in length and harbour three methylase genes, two 22 of which demonstrate cytosine specificity. Transformation of the Vibrio cholerae 23 strain C6706 with the IncA/C plasmid pVC211 resulted in a significant relabelling of 24 the methylation patterns on the host chromosomes. The new methylation patterns 25 induced by transformation with IncA/C plasmid were accepted by the restriction 26 enzymes of the host's restriction modification (RM) system. These data uncover a 27 novel mechanism by which plasmids can be compatible with a host's RM system and 28 suggest a possible reason that plasmids of the IncA/C family are broad-host-range. 30Author summary: 31 Antibiotic resistance of bacteria is a growing serious problem worldwidely and 32 the horizontal transfer of multi-drug resistance genes mediated by plasmids within 33 and between species of bacteria is the main reason. In the researches of multi-drug 34 resistance of Vibrio cholerae, I have isolated several IncA/C plasmids. What 35 impressed me most is their ability to accumulate the resistant genes. Moreover, they 36 can transfer with high frequency and are stable in several bacterial species. There are 37 at least three Tra regions on the IncA/C plasmid which containing components of the 38 Type 4 Secretion System and are important for conjugative transfer of plasmids. So 39 the horizontal transfer ability of IncA/C plasmids is reasonable. There are three 40 methylase genes on the small genome of IncA/C plasmids, which demonstrate 41 cytosine specificity and are seldom in bacteria. Their modification target and roles are 42interesting. Here, we analysed the methylation profiles of the host V. choerae induced 43 by the plasmid pVC211 and found that they were completely changed. In addition to 44 replicons, this may be a novel mechanism that plasmid cross the barrier of the host's 45 RM system and become broad-host range. Changing the activity of methylase in 46 IncA/C plasmids may be a new way to affect the stability of IncA/C plasmids to 47 51 plasmid-incompatible groups (Inc) and mediate the dissemination of multi-drug 52 resistance in bacteria [1,2]. Both of the plasmid pIP1202, which has high resistance to 53 at least eight antibiotics isolated from Yersinia pestis IP275 in 1995 [3], and the 54 plasmid of NDM-1 super-resistant bacteria in India, Bangladesh, Pakistan, Britain and 55 the United States in August 2010 [4] are IncA/C family plasmids and have aroused 56 great concern in public health and bioterrorism. IncA/C plasmids have great ability to 57 accumulate antibiotic resistant genes. There are many resistance genes of rifampicin, 58 erythromycin, streptomycin, chloramphenicol, sulfonamides and disinfectants 59 routinely harbored on the plasmids [5], as well as a variety of beta-lactamase genes. 60 For example, the pNDM-1_Dok01, pNDM102337, pND...

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A role for the bacterial GATC methylome in antibiotic stress survival

Cited by 95 publications

References 75 publications

Genomewide Dam Methylation in Escherichia coli during Long-Term Stationary Phase

Genomewide Dam Methylation in Escherichia coli during Long-Term Stationary Phase

Profiling of Human Gut Virome with Oxford Nanopore Technology

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

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