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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 -
Annual Review of Microbiology Sep 2023Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular... (Review)
Review
Mobile genetic elements are key to the evolution of bacteria and traits that affect host and ecosystem health. Here, we use a framework of a hierarchical and modular system that scales from genes to populations to synthesize recent findings on mobile genetic elements (MGEs) of bacteria. Doing so highlights the role that emergent properties of flexibility, robustness, and genetic capacitance of MGEs have on the evolution of bacteria. Some of their traits can be stored, shared, and diversified across different MGEs, taxa of bacteria, and time. Collectively, these properties contribute to maintaining functionality against perturbations while allowing changes to accumulate in order to diversify and give rise to new traits. These properties of MGEs have long challenged our abilities to study them. Implementation of new technologies and strategies allows for MGEs to be analyzed in new and powerful ways.
Topics: Ecosystem; Bacteria; Phenotype; Interspersed Repetitive Sequences
PubMed: 37437216
DOI: 10.1146/annurev-micro-032521-022006 -
Trends in Cancer Jul 2021Retrotransposons have been known as major sources of genomic instability that trigger and promote cancer development. In a recent study, Gu et al. revealed that MPP8...
Retrotransposons have been known as major sources of genomic instability that trigger and promote cancer development. In a recent study, Gu et al. revealed that MPP8 deficiency impeded tumor development through reactivation long interspersed element-1 (LINE-1 or L1) retrotransposons in acute myeloid leukemia (AML), suggesting a tumor-suppressive role for retrotransposons.
Topics: Genomic Instability; Humans; Long Interspersed Nucleotide Elements; Neoplasms; Retroelements
PubMed: 33992534
DOI: 10.1016/j.trecan.2021.04.004 -
Genome Research Sep 2023Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its...
Mice harbor ∼2800 intact copies of the retrotransposon Long Interspersed Element 1 (L1). The in vivo retrotransposition capacity of an L1 copy is defined by both its sequence integrity and epigenetic status, including DNA methylation of the monomeric units constituting young mouse L1 promoters. Locus-specific L1 methylation dynamics during development may therefore elucidate and explain spatiotemporal niches of endogenous retrotransposition but remain unresolved. Here, we interrogate the retrotransposition efficiency and epigenetic fate of source (donor) L1s, identified as mobile in vivo. We show that promoter monomer loss consistently attenuates the relative retrotransposition potential of their offspring (daughter) L1 insertions. We also observe that most donor/daughter L1 pairs are efficiently methylated upon differentiation in vivo and in vitro. We use Oxford Nanopore Technologies (ONT) long-read sequencing to resolve L1 methylation genome-wide and at individual L1 loci, revealing a distinctive "smile" pattern in methylation levels across the L1 promoter region. Using Pacific Biosciences (PacBio) SMRT sequencing of L1 5' RACE products, we then examine DNA methylation dynamics at the mouse L1 promoter in parallel with transcription start site (TSS) distribution at locus-specific resolution. Together, our results offer a novel perspective on the interplay between epigenetic repression, L1 evolution, and genome stability.
Topics: Mice; Animals; Embryonic Development; Long Interspersed Nucleotide Elements; Retroelements; DNA Methylation; Promoter Regions, Genetic
PubMed: 37798118
DOI: 10.1101/gr.278003.123 -
Biochimica Et Biophysica Acta. Gene... Feb 2020Bacteria exhibit an amazing diversity of mechanisms controlling gene expression to both maintain essential functions and modulate accessory functions in response to... (Review)
Review
Bacteria exhibit an amazing diversity of mechanisms controlling gene expression to both maintain essential functions and modulate accessory functions in response to environmental cues. Over the years, it has become clear that bacterial regulation of gene expression is still far from fully understood. This review focuses on antisense RNAs (asRNAs), a class of RNA regulators defined by their location in cis and their perfect complementarity with their targets, as opposed to small RNAs (sRNAs) which act in trans with only short regions of complementarity. For a long time, only few functional asRNAs in bacteria were known and were almost exclusively found on mobile genetic elements (MGEs), thus, their importance among the other regulators was underestimated. However, the extensive application of transcriptomic approaches has revealed the ubiquity of asRNAs in bacteria. This review aims to present the landscape of studied asRNAs in bacteria by comparing 67 characterized asRNAs from both Gram-positive and Gram-negative bacteria. First we describe the inherent ambiguity in the existence of asRNAs in bacteria, second, we highlight their diversity and their involvement in all aspects of bacterial life. Finally we compare their location and potential mode of action toward their target between Gram-negative and Gram-positive bacteria and present tendencies and exceptions that could lead to a better understanding of asRNA functions.
Topics: Gene Expression Regulation, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Interspersed Repetitive Sequences; RNA, Antisense
PubMed: 31935527
DOI: 10.1016/j.bbagrm.2020.194489 -
Viruses Aug 2019The last decade has been marked by two eminent discoveries that have changed our perception of the virology field: The discovery of giant viruses and a distinct new... (Review)
Review
The last decade has been marked by two eminent discoveries that have changed our perception of the virology field: The discovery of giant viruses and a distinct new class of viral agents that parasitize their viral factories, the virophages. Coculture and metagenomics have actively contributed to the expansion of the virophage family by isolating dozens of new members. This increase in the body of data on virophage not only revealed the diversity of the virophage group, but also the relevant ecological impact of these small viruses and their potential role in the dynamics of the microbial network. In addition, the isolation of virophages has led us to discover previously unknown features displayed by their host viruses and cells. In this review, we present an update of all the knowledge on the isolation, biology, genomics, and morphological features of the virophages, a decade after the discovery of their first member, the Sputnik virophage. We discuss their parasitic lifestyle as viruses of the giant virus factories, genetic parasites of their genomes, and then their role as a key component or target for some host defense mechanisms during the tripartite virophage-giant virus-host cell interaction. We also present the latest advances regarding their origin, classification, and definition that have been widely discussed.
Topics: Animals; Biological Evolution; Genome, Viral; Genomics; Giant Viruses; History, 21st Century; Host-Pathogen Interactions; Humans; Interspersed Repetitive Sequences; Life Cycle Stages; Metagenomics; Research; Virology; Virophages
PubMed: 31398856
DOI: 10.3390/v11080733 -
Cell Jan 2023Despite being typically perceived as "clonal" organisms, bacteria and archaea possess numerous mechanisms to share and co-opt genetic material from other lineages....
Despite being typically perceived as "clonal" organisms, bacteria and archaea possess numerous mechanisms to share and co-opt genetic material from other lineages. Several mechanisms for horizontal gene transfer have been discovered, but the high mosaicity observed in many bacterial genomes outscales that explained by known mechanisms, hinting at yet undiscovered processes. In this issue of Cell, Hackl et al. introduce a new category of mobile genetic elements called tycheposons, providing a novel mechanism that contributes to the prodigious genomic diversity within microbial populations. The discovery and characterization of tycheposons prompts a reevaluation of microbial diversification in complex environments.
Topics: Archaea; Bacteria; Gene Transfer, Horizontal; Genome, Bacterial; Interspersed Repetitive Sequences
PubMed: 36608658
DOI: 10.1016/j.cell.2022.12.001 -
Nature Cell Biology Jan 2022
Topics: Endogenous Retroviruses
PubMed: 34961795
DOI: 10.1038/s41556-021-00758-y -
Methods in Molecular Biology (Clifton,... 2023The ongoing mobilization of active non-long terminal repeat (LTR) retrotransposons continues to impact the genomes of most mammals, including humans and rodents. Non-LTR...
The ongoing mobilization of active non-long terminal repeat (LTR) retrotransposons continues to impact the genomes of most mammals, including humans and rodents. Non-LTR retrotransposons mobilize using an intermediary RNA and a copy-and-paste mechanism termed retrotransposition. Non-LTR retrotransposons are subdivided into long and short interspersed elements (LINEs and SINEs, respectively), depending on their size and autonomy; while active class 1 LINEs (LINE-1s or L1s) encode the enzymatic machinery required to mobilize in cis, active SINEs use the enzymatic machinery of active LINE-1s to mobilize in trans. The mobilization mechanism used by LINE-1s/SINEs was exploited to develop ingenious plasmid-based retrotransposition assays in cultured cells, which typically exploit a reporter gene that can only be activated after a round of retrotransposition. Retrotransposition assays, in cis or in trans, are instrumental tools to study the biology of mammalian LINE-1s and SINEs. In fact, these and other biochemical/genetic assays were used to uncover that endogenous mammalian LINE-1s/SINEs naturally retrotranspose during early embryonic development. However, embryonic stem cells (ESCs) are typically used as a cellular model in these and other studies interrogating LINE-1/SINE expression/regulation during early embryogenesis. Thus, human and mouse ESCs represent an excellent model to understand how active retrotransposons are regulated and how their activity impacts the germline. Here, we describe robust and quantitative protocols to study human/mouse LINE-1 (in cis) and SINE (in trans) retrotransposition using (human and mice) ESCs. These protocols are designed to study the mobilization of active non-LTR retrotransposons in a cellular physiologically relevant context.
Topics: Female; Pregnancy; Humans; Mice; Animals; Retroelements; Long Interspersed Nucleotide Elements; Embryonic Stem Cells; Short Interspersed Nucleotide Elements; Biological Assay; Mammals
PubMed: 36449167
DOI: 10.1007/978-1-0716-2883-6_13 -
International Journal of Molecular... May 2021Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that can infect the peripheral and central nervous systems, and it has been implicated in... (Review)
Review
Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that can infect the peripheral and central nervous systems, and it has been implicated in demyelinating and neurodegenerative processes. Transposable elements (TEs) are DNA sequences that can move from one genomic location to another. TEs have been linked to several diseases affecting the central nervous system (CNS), including multiple sclerosis (MS), a demyelinating disease of unknown etiology influenced by genetic and environmental factors. Exogenous viral transactivators may activate certain retrotransposons or class I TEs. In this context, several herpesviruses have been linked to MS, and one of them, HSV-1, might act as a risk factor by mediating processes such as molecular mimicry, remyelination, and activity of endogenous retroviruses (ERVs). Several herpesviruses have been involved in the regulation of human ERVs (HERVs), and HSV-1 in particular can modulate HERVs in cells involved in MS pathogenesis. This review exposes current knowledge about the relationship between HSV-1 and human ERVs, focusing on their contribution as a risk factor for MS.
Topics: Animals; Biological Evolution; DNA Transposable Elements; Demyelinating Diseases; Disease Susceptibility; Endogenous Retroviruses; Herpes Simplex; Herpesvirus 1, Human; Humans; Multiple Sclerosis; Retroelements
PubMed: 34072259
DOI: 10.3390/ijms22115738