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Microbiology Spectrum Jul 2019Enterococci are unusually well adapted for survival and persistence in a variety of adverse environments, including on inanimate surfaces in the hospital environment and... (Review)
Review
Enterococci are unusually well adapted for survival and persistence in a variety of adverse environments, including on inanimate surfaces in the hospital environment and at sites of infection. This intrinsic ruggedness undoubtedly played a role in providing opportunities for enterococci to interact with other overtly drug-resistant microbes and acquire additional resistances on mobile elements. The rapid rise of antimicrobial resistance among hospital-adapted enterococci has rendered hospital-acquired infections a leading therapeutic challenge. With about a quarter of a genome of additional DNA conveyed by mobile elements, there are undoubtedly many more properties that have been acquired that help enterococci persist and spread in the hospital setting and cause diseases that have yet to be defined. Much remains to be learned about these ancient and rugged microbes, particularly in the area of pathogenic mechanisms involved with human diseases.
Topics: Animals; Enterococcus; Gram-Positive Bacterial Infections; Humans; Interspersed Repetitive Sequences; Virulence
PubMed: 31298205
DOI: 10.1128/microbiolspec.GPP3-0053-2018 -
Microbiology Spectrum Jul 2018For nearly a century the use of antibiotics to treat infectious diseases has benefited human and animal health. In recent years there has been an increase in the... (Review)
Review
For nearly a century the use of antibiotics to treat infectious diseases has benefited human and animal health. In recent years there has been an increase in the emergence of antibiotic-resistant bacteria, in part attributed to the overuse of compounds in clinical and farming settings. The genus currently comprises 17 recognized species found throughout the environment. is the etiological agent of listeriosis in humans and many vertebrate species, including birds, whereas causes infections mainly in ruminants. is the third-most-common cause of death from food poisoning in humans, and infection occurs in at-risk groups, including pregnant women, newborns, the elderly, and immunocompromised individuals.
Topics: Aged; Animals; Animals, Domestic; Anti-Infective Agents; Drug Resistance, Bacterial; Farms; Female; Food Microbiology; Foodborne Diseases; Humans; Infant, Newborn; Interspersed Repetitive Sequences; Listeria; Listeria monocytogenes; Listeriosis; Pregnancy
PubMed: 30027884
DOI: 10.1128/microbiolspec.ARBA-0031-2017 -
Cell Aug 2022Non-allelic recombination between homologous repetitive elements contributes to evolution and human genetic disorders. Here, we combine short- and long-DNA read...
Non-allelic recombination between homologous repetitive elements contributes to evolution and human genetic disorders. Here, we combine short- and long-DNA read sequencing of repeat elements with a new bioinformatics pipeline to show that somatic recombination of Alu and L1 elements is widespread in the human genome. Our analysis uncovers tissue-specific non-allelic homologous recombination hallmarks; moreover, we find that centromeres and cancer-associated genes are enriched for retroelements that may act as recombination hotspots. We compare recombination profiles in human-induced pluripotent stem cells and differentiated neurons and find that the neuron-specific recombination of repeat elements accompanies chromatin changes during cell-fate determination. Finally, we report that somatic recombination profiles are altered in Parkinson's and Alzheimer's disease, suggesting a link between retroelement recombination and genomic instability in neurodegeneration. This work highlights a significant contribution of the somatic recombination of repeat elements to genomic diversity in health and disease.
Topics: Alu Elements; Genome, Human; Homologous Recombination; Humans; Long Interspersed Nucleotide Elements; Repetitive Sequences, Nucleic Acid; Retroelements
PubMed: 35882231
DOI: 10.1016/j.cell.2022.06.032 -
Cell Research Jun 2021Organization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved and relatively stable during lineage differentiation. In an effort...
Organization of the genome into euchromatin and heterochromatin appears to be evolutionarily conserved and relatively stable during lineage differentiation. In an effort to unravel the basic principle underlying genome folding, here we focus on the genome itself and report a fundamental role for L1 (LINE1 or LINE-1) and B1/Alu retrotransposons, the most abundant subclasses of repetitive sequences, in chromatin compartmentalization. We find that homotypic clustering of L1 and B1/Alu demarcates the genome into grossly exclusive domains, and characterizes and predicts Hi-C compartments. Spatial segregation of L1-rich sequences in the nuclear and nucleolar peripheries and B1/Alu-rich sequences in the nuclear interior is conserved in mouse and human cells and occurs dynamically during the cell cycle. In addition, de novo establishment of L1 and B1 nuclear segregation is coincident with the formation of higher-order chromatin structures during early embryogenesis and appears to be critically regulated by L1 and B1 transcripts. Importantly, depletion of L1 transcripts in embryonic stem cells drastically weakens homotypic repeat contacts and compartmental strength, and disrupts the nuclear segregation of L1- or B1-rich chromosomal sequences at genome-wide and individual sites. Mechanistically, nuclear co-localization and liquid droplet formation of L1 repeat DNA and RNA with heterochromatin protein HP1α suggest a phase-separation mechanism by which L1 promotes heterochromatin compartmentalization. Taken together, we propose a genetically encoded model in which L1 and B1/Alu repeats blueprint chromatin macrostructure. Our model explains the robustness of genome folding into a common conserved core, on which dynamic gene regulation is overlaid across cells.
Topics: Animals; Cluster Analysis; Long Interspersed Nucleotide Elements; Mice; RNA; Repetitive Sequences, Nucleic Acid; Retroelements
PubMed: 33514913
DOI: 10.1038/s41422-020-00466-6 -
Current Genetics Dec 2020Bacteria and other prokaryotes evolve primarily through rapid changes in their gene content by quickly losing and gaining genes whenever an ecological opportunity... (Review)
Review
Bacteria and other prokaryotes evolve primarily through rapid changes in their gene content by quickly losing and gaining genes whenever an ecological opportunity emerges. As gene loss and horizontal gene transfer (HGT) appear to be the most common events across the prokaryotic tree of life, we need to think beyond gradual sequence evolution if we wish to understand the microbial world. Especially genes that reside on mobile genetic elements (MGEs) may spread much more rapidly through a microbial population than genes that reside on the bacterial chromosome. This raises the question: why are some genes associated with MGEs, while others are not? Here, I briefly review a recently proposed class of genes for which we have coined the term "rescuable genes". The fitness effect of carrying these genes is so small, either constantly or on average, that they are prone to be lost from a microbial population. I argue that HGT, even when costly to the individual cells, may play an important role in maintaining these rescuable genes in microbial communities.
Topics: Bacteria; Chromosomes, Bacterial; Evolution, Molecular; Gene Transfer, Horizontal; Interspersed Repetitive Sequences; Prokaryotic Cells
PubMed: 32880674
DOI: 10.1007/s00294-020-01104-9 -
Gut Microbes Nov 2020Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is... (Review)
Review
Antimicrobial resistance is one of the largest threats to global health and imposes substantial burdens in terms of morbidity, mortality, and economic costs. The gut is a key conduit for the genesis and spread of antimicrobial resistance in enteric bacterial pathogens. Distinct bacterial species that cause enteric disease can exist as invasive enteropathogens that immediately evoke gastrointestinal distress, or pathobionts that can arise from established bacterial commensals to inflict dysbiosis and disease. Furthermore, various environmental reservoirs and stressors facilitate the evolution and transmission of resistance. In this review, we present a comprehensive discussion on circulating resistance profiles and gene mobilization strategies of the most problematic species of enteric bacterial pathogens. Importantly, we present emerging approaches toward surveillance of pathogens and their resistance elements as well as promising treatment strategies that can circumvent common resistance mechanisms.
Topics: Anti-Bacterial Agents; Bacteria; Biological Evolution; Drug Resistance, Bacterial; Dysbiosis; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Interspersed Repetitive Sequences; Metagenomics
PubMed: 32772817
DOI: 10.1080/19490976.2020.1799654 -
Microbiology Spectrum Apr 2015The integron is a powerful system which, by capturing, stockpiling, and rearranging new functions carried by gene encoding cassettes, confers upon bacteria a rapid... (Review)
Review
The integron is a powerful system which, by capturing, stockpiling, and rearranging new functions carried by gene encoding cassettes, confers upon bacteria a rapid adaptation capability in changing environments. Chromosomally located integrons (CI) have been identified in a large number of environmental Gram-negative bacteria. Integron evolutionary history suggests that these sedentary CIs acquired mobility among bacterial species through their association with transposable elements and conjugative plasmids. As a result of massive antibiotic use, these so-called mobile integrons are now widespread in clinically relevant bacteria and are considered to be the principal agent in the emergence and rise of antibiotic multiresistance in Gram-negative bacteria. Cassette rearrangements are catalyzed by the integron integrase, a site-specific tyrosine recombinase. Central to these reactions is the single-stranded DNA nature of one of the recombination partners, the attC site. This makes the integron a unique recombination system. This review describes the current knowledge on this atypical recombination mechanism, its implications in the reactions involving the different types of sites, attC and attI, and focuses on the tight regulation exerted by the host on integron activity through the control of attC site folding. Furthermore, cassette and integrase expression are also highly controlled by host regulatory networks and the bacterial stress (SOS) response. These intimate connections to the host make the integron a genetically stable and efficient system, granting the bacteria a low cost, highly adaptive evolution potential "on demand".
Topics: Adaptation, Biological; Attachment Sites, Microbiological; Gene Rearrangement; Gene Transfer, Horizontal; Gram-Negative Bacteria; Integrons; Interspersed Repetitive Sequences; Recombination, Genetic
PubMed: 26104695
DOI: 10.1128/microbiolspec.MDNA3-0019-2014 -
Methods in Molecular Biology (Clifton,... 2018Chromothripsis is a mutational event driven by tens to hundreds of double-stranded DNA breaks which occur in a single event between a limited number of chromosomes....
Chromothripsis is a mutational event driven by tens to hundreds of double-stranded DNA breaks which occur in a single event between a limited number of chromosomes. Following chromosomal shattering, DNA fragments are stitched together in a seemingly random manner resulting in complex genomic rearrangements including sequence shuffling, deletions, and inversions of varying size. This genomic catastrophe has been observed in cancer genomes and the genomes of patients harboring developmental and congenital defects. The mechanisms catalyzing DNA breakage and coordinating the "random" assembly of genomic fragments are actively being investigated. Recently, retrotransposons-a type of "jumping gene"-have been implicated as one means to generate double-stranded DNA breaks during chromothripsis and as sequences which can contribute to the final configuration of the derived chromosomes. In this methods chapter, I discuss how to apply available bioinformatic tools and the hallmarks of retrotransposon mobilization to breakpoint junctions to assess the role for active and inactive retrotransposon sequences in chromothriptic events.
Topics: Alu Elements; Chromothripsis; Genome, Human; Homologous Recombination; Humans; Long Interspersed Nucleotide Elements; Mutagenesis, Insertional; Retroelements; Sequence Deletion; Sequence Inversion
PubMed: 29564824
DOI: 10.1007/978-1-4939-7780-2_11 -
Microbial Biotechnology Jan 2024Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids,... (Review)
Review
Mobile genetic elements (MGEs) are crucial for horizontal gene transfer (HGT) in bacteria and facilitate their rapid evolution and adaptation. MGEs include plasmids, integrative and conjugative elements, transposons, insertion sequences and bacteriophages. Notably, the spread of antimicrobial resistance genes (ARGs), which poses a serious threat to public health, is primarily attributable to HGT through MGEs. This mini-review aims to provide an overview of the mechanisms by which MGEs mediate HGT in microbes. Specifically, the behaviour of conjugative plasmids in different environments and conditions was discussed, and recent methodologies for tracing the dynamics of MGEs were summarised. A comprehensive understanding of the mechanisms underlying HGT and the role of MGEs in bacterial evolution and adaptation is important to develop strategies to combat the spread of ARGs.
Topics: Interspersed Repetitive Sequences; Gene Transfer, Horizontal; Plasmids; Bacteria; Bacteriophages; Anti-Bacterial Agents
PubMed: 38226780
DOI: 10.1111/1751-7915.14408 -
Epigenetics & Chromatin Jun 2021DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability... (Review)
Review
BACKGROUND
DNA methylation is an epigenetic chromatin mark that allows heterochromatin formation and gene silencing. It has a fundamental role in preserving genome stability (including chromosome stability) by controlling both gene expression and chromatin structure. Therefore, the onset of an incorrect pattern of DNA methylation is potentially dangerous for the cells. This is particularly important with respect to repetitive elements, which constitute the third of the human genome.
MAIN BODY
Repetitive sequences are involved in several cell processes, however, due to their intrinsic nature, they can be a source of genome instability. Thus, most repetitive elements are usually methylated to maintain a heterochromatic, repressed state. Notably, there is increasing evidence showing that repetitive elements (satellites, long interspersed nuclear elements (LINEs), Alus) are frequently hypomethylated in various of human pathologies, from cancer to psychiatric disorders. Repetitive sequences' hypomethylation correlates with chromatin relaxation and unscheduled transcription. If these alterations are directly involved in human diseases aetiology and how, is still under investigation.
CONCLUSIONS
Hypomethylation of different families of repetitive sequences is recurrent in many different human diseases, suggesting that the methylation status of these elements can be involved in preservation of human health. This provides a promising point of view towards the research of therapeutic strategies focused on specifically tuning DNA methylation of DNA repeats.
Topics: Chromatin; DNA Methylation; Epigenomics; Humans; Long Interspersed Nucleotide Elements; Repetitive Sequences, Nucleic Acid
PubMed: 34082816
DOI: 10.1186/s13072-021-00400-z