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Nature Reviews. Genetics Feb 2020All cellular life forms are afflicted by diverse genetic parasites, including viruses and other types of mobile genetic elements (MGEs), and have evolved multiple,... (Review)
Review
All cellular life forms are afflicted by diverse genetic parasites, including viruses and other types of mobile genetic elements (MGEs), and have evolved multiple, diverse defence systems that protect them from MGE assault via different mechanisms. Here, we provide our perspectives on how recent evidence points to tight evolutionary connections between MGEs and defence systems that reach far beyond the proverbial arms race. Defence systems incur a fitness cost for the hosts; therefore, at least in prokaryotes, horizontal mobility of defence systems, mediated primarily by MGEs, is essential for their persistence. Moreover, defence systems themselves possess certain features of selfish elements. Common components of MGEs, such as site-specific nucleases, are 'guns for hire' that can also function as parts of defence mechanisms and are often shuttled between MGEs and defence systems. Thus, evolutionary and molecular factors converge to mould the multifaceted, inextricable connection between MGEs and anti-MGE defence systems.
Topics: Biological Evolution; Evolution, Molecular; Gene Transfer, Horizontal; Host-Pathogen Interactions; Interspersed Repetitive Sequences
PubMed: 31611667
DOI: 10.1038/s41576-019-0172-9 -
Cold Spring Harbor Protocols Dec 2016Prokaryotes use diverse strategies to improve fitness in the face of different environmental threats and stresses, including those posed by mobile genetic elements...
Prokaryotes use diverse strategies to improve fitness in the face of different environmental threats and stresses, including those posed by mobile genetic elements (e.g., bacteriophages and plasmids). To defend against these elements, many bacteria and archaea use elegant, RNA-directed, nucleic acid-targeting adaptive restriction machineries called CRISPR -: Cas (CRISPR-associated) systems. While providing an effective defense against foreign genetic elements, these systems have also been observed to play critical roles in regulating bacterial physiology during environmental stress. Increasingly, CRISPR-Cas systems, in particular the Type II systems containing the Cas9 endonuclease, have been exploited for their ability to bind desired nucleic acid sequences, as well as direct sequence-specific cleavage of their targets. Cas9-mediated genome engineering is transcending biological research as a versatile and portable platform for manipulating genetic content in myriad systems. Here, we present a systematic overview of CRISPR-Cas history and biology, highlighting the revolutionary tools derived from these systems, which greatly expand the molecular biologists' toolkit.
Topics: Archaea; Bacteria; CRISPR-Cas Systems; Gene Targeting; Gene Transfer, Horizontal; Interspersed Repetitive Sequences
PubMed: 27934695
DOI: 10.1101/pdb.top088849 -
Critical Reviews in Oncogenesis 2015Gene therapy for cancer is a still evolving approach that resulted from a long history of studies into genetic modification of organisms. The fascination with... (Review)
Review
Gene therapy for cancer is a still evolving approach that resulted from a long history of studies into genetic modification of organisms. The fascination with manipulating gene products has spanned hundreds if not thousands of years, beginning with observations of the hereditary nature of traits in plants and culminating to date in the alteration of genetic makeup in humans via modern technology. From early discoveries noting the potential for natural mobility of genetic material to the culmination of clinical trials in a variety of disease, gene transfer has had an eventful and sometimes tumultuous course. Within the present review is a brief history of the biology of gene transfer, how it came to be applied to genetic diseases, and its early applications to cancer therapies. Some of the different types of methods used to modify cells, the theories behind the approaches, and some of the limitations encountered along the way are reviewed.
Topics: Animals; Female; Genetic Therapy; Humans; Interspersed Repetitive Sequences; Male; Neoplasms
PubMed: 27279244
DOI: 10.1615/CritRevOncog.v20.i5-6.180 -
Current Opinion in Microbiology Aug 2017The staphylococcal pathogenicity islands (SaPIs) are highly mobile 15kb genomic islands that carry superantigen genes and other virulence factors and are mobilized by... (Review)
Review
The staphylococcal pathogenicity islands (SaPIs) are highly mobile 15kb genomic islands that carry superantigen genes and other virulence factors and are mobilized by helper phages. Helper phages counteract the SaPI repressor to induce the SaPI replication cycle, resulting in encapsidation in phage like particles, enabling high frequency transfer. The SaPIs split from a protophage lineage in the distant past, have evolved a variety of novel and salient features, and have become an invaluable component of the staphylococcal genome. This review focuses on recent studies describing three different mechanisms of SaPI interference with helper phage reproduction and other studies demonstrating that helper phage mutations to resistance against this interference impact phage evolution. Also described are recent results showing that SaPIs contribute in a major way to lateral transfer of host genes as well as enabling their own transfer. SaPI-like elements, readily identifiable in the bacterial genome, are widespread throughout the Gram-positive cocci, though functionality has thus far been demonstrated for only a single one of these.
Topics: Bacteriophages; Gene Transfer, Horizontal; Genome, Bacterial; Genomic Islands; Interspersed Repetitive Sequences; Staphylococcus; Transduction, Genetic; Virulence Factors
PubMed: 29100762
DOI: 10.1016/j.mib.2017.08.001 -
Current Opinion in Microbiology Dec 2022Studies of viral adaptation have focused on the selective pressures imposed by hosts. However, there is increasing evidence that interactions between viruses, cells, and... (Review)
Review
Studies of viral adaptation have focused on the selective pressures imposed by hosts. However, there is increasing evidence that interactions between viruses, cells, and other mobile genetic elements are determinant to the success of infections. These interactions are often associated with antagonism and competition, but sometimes involve cooperation or parasitism. We describe two key types of interactions - defense systems and genetic regulation - that allow the partners of the interaction to destroy or control the others. These interactions evolve rapidly by genetic exchanges, including among competing partners. They are sometimes followed by functional diversification. Gene exchanges also facilitate the emergence of cross-talk between elements in the same bacterium. In the end, these processes produce multilayered networks of interactions that shape the outcome of viral infections.
Topics: Bacteriophages; Viruses; Bacteria; Symbiosis; Interspersed Repetitive Sequences
PubMed: 36335712
DOI: 10.1016/j.mib.2022.102230 -
Plasmid Sep 2018Multi-antibiotic resistant (MAR) bacteria cost billions in medical care and tens of thousands of lives annually but perennial calls to limit agricultural and other... (Review)
Review
Multi-antibiotic resistant (MAR) bacteria cost billions in medical care and tens of thousands of lives annually but perennial calls to limit agricultural and other misuse of antibiotics and to fund antibiotic discovery have not slowed this MAR deluge. Since mobile genetic elements (MGEs) stitch single antibiotic resistance genes into clinically significant MAR arrays, it is high time to focus on how MGEs generate MAR and how disabling them could ameliorate the MAR problem. However, to consider only antibiotics as the drivers of MAR is to miss the significant impact of exposure to non-antibiotic toxic chemicals, specifically metals, on the persistence and spread of MAR. Toxic metals were among the earliest discovered targets of plasmid-encoded resistance genes. Recent genomic epidemiology clearly demonstrated the co-prevalence of metal resistances and antibiotic multi-resistance, uniquely in humans and domestic animals. Metal resistances exploit the same, ancient "transportation infrastructure" of plasmids, transposons, and integrons that spread the antibiotic resistance genes and will continue to do so even if all antibiotic misuse were stopped today and new antibiotics were flowing from the pipeline monthly. In a key experiment with primates, continuous oral exposure to mercury (Hg) released from widely used dental amalgam fillings co-selected for MAR bacteria in the oral and fecal commensal microbiomes and, most importantly, when amalgams were replaced with non-metal fillings, MAR bacteria declined dramatically. Could that also be happening on the larger public health scale as use of amalgam restorations is curtailed or banned in many countries? This commentary covers salient past and recent findings of key metal-antibiotic resistance associations and proposes that the shift from phenotyping to genotyping in surveillance of resistance loci will allow a test of whether declining exposure to this leading source of Hg is accompanied by a decline in MAR compared to countries where amalgam is still used. If this hypothesis is correct, the limited success of antibiotic stewardship practices may be because MAR is also being driven by continuous, daily exposure to Hg, a non-antibiotic toxicant widely used in humans.
Topics: Antimicrobial Stewardship; Bacteria; Dental Amalgam; Drug Resistance, Multiple, Bacterial; Humans; Interspersed Repetitive Sequences; Mercury; Metals; Plasmids
PubMed: 30193909
DOI: 10.1016/j.plasmid.2018.08.003 -
Viruses Oct 2019Horizontal transfer of mobile genetic elements (MGEs) is a key aspect of the evolution of bacterial pathogens. Transduction by bacteriophages is especially important in... (Review)
Review
Horizontal transfer of mobile genetic elements (MGEs) is a key aspect of the evolution of bacterial pathogens. Transduction by bacteriophages is especially important in this process. Bacteriophages-which assemble a machinery for efficient encapsidation and transfer of genetic material-often transfer MGEs and other chromosomal DNA in a more-or-less nonspecific low-frequency process known as generalized transduction. However, some MGEs have evolved highly specific mechanisms to take advantage of bacteriophages for their own propagation and high-frequency transfer while strongly interfering with phage production-"molecular piracy". These mechanisms include the ability to sense the presence of a phage entering lytic growth, specific recognition and packaging of MGE genomes into phage capsids, and the redirection of the phage assembly pathway to form capsids with a size more appropriate for the size of the MGE. This review focuses on the process of assembly redirection, which has evolved convergently in many different MGEs from across the bacterial universe. The diverse mechanisms that exist suggest that size redirection is an evolutionarily advantageous strategy for many MGEs.
Topics: Bacteriophages; Capsid; Capsid Proteins; Firmicutes; Genomic Islands; Gram-Negative Facultatively Anaerobic Rods; Interspersed Repetitive Sequences; Microbial Interactions; Staphylococcus Phages; Staphylococcus aureus; Transduction, Genetic; Virulence Factors; Virus Assembly
PubMed: 31683607
DOI: 10.3390/v11111003 -
Current Opinion in Microbiology Aug 2017Although the phenomenon of transposition has been known for over 60 years, its overarching importance in modifying and streamlining genomes took some time to recognize.... (Review)
Review
Although the phenomenon of transposition has been known for over 60 years, its overarching importance in modifying and streamlining genomes took some time to recognize. In spite of a robust understanding of transposition of some TE, there remain a number of important TE groups with potential high genome impact and unknown transposition mechanisms and yet others, only recently identified by bioinformatics, yet to be formally confirmed as mobile. Here, we point to some areas of limited understanding concerning well established important TE groups with DDE Tpases, to address central gaps in our knowledge of characterised Tn with other types of Tpases and finally, to highlight new potentially mobile DNA species. It is not exhaustive. Examples have been chosen to provide encouragement in the continued exploration of the considerable prokaryotic mobilome especially in light of the current threat to public health posed by the spread of multiple Ab.
Topics: Archaea; Bacteria; Evolution, Molecular; Interspersed Repetitive Sequences; Recombination, Genetic
PubMed: 28683354
DOI: 10.1016/j.mib.2017.06.005 -
Trends in Microbiology Jul 2024Phages and plasmids are discrete mobile genetic elements (MGEs) with critical roles in gene dissemination across bacteria but limited scope for exchanging DNA between...
Phages and plasmids are discrete mobile genetic elements (MGEs) with critical roles in gene dissemination across bacteria but limited scope for exchanging DNA between them. By investigating recent gene-sharing events, Pfeifer and Rocha describe how the hybrid elements phage-plasmids (P-Ps) promote gene flow between MGE types and evolve into new ones.
Topics: Bacteriophages; Plasmids; Interspersed Repetitive Sequences; Bacteria; Gene Transfer, Horizontal; Gene Flow; Evolution, Molecular
PubMed: 38755022
DOI: 10.1016/j.tim.2024.04.014 -
PloS One 2021Antibiotic resistance genes (ARGs) are emerging contaminants causing serious global health concern. Interventions to address this concern include improving our...
Antibiotic resistance genes (ARGs) are emerging contaminants causing serious global health concern. Interventions to address this concern include improving our understanding of methods for treating waste material of human and animal origin that are known to harbor ARGs. Anaerobic digestion is a commonly used process for treating dairy manure, and although effective in reducing ARGs, its mechanism of action is not clear. In this study, we used three ARGs to conducted a longitudinal bench scale anaerobic digestion experiment with various temperatures (28, 36, 44, and 52°C) in triplicate using fresh dairy manure for 30 days to evaluate the reduction of gene abundance. Three ARGs and two mobile genetic elements (MGEs) were studied: sulfonamide resistance gene (sulII), tetracycline resistance genes (tetW), macrolide-lincosamide-streptogramin B (MLSB) superfamily resistance genes (ermF), class 1 integrase gene (intI1), and transposase gene (tnpA). Genes were quantified by real-time quantitative PCR. Results show that the thermophilic anaerobic digestion (52°C) significantly reduced (p < 0.05) the absolute abundance of sulII (95%), intI1 (95%), tnpA (77%) and 16S rRNA gene (76%) after 30 days of digestion. A modified Collins-Selleck model was used to fit the decay curve, and results suggest that the gene reduction during the startup phase of anaerobic digestion (first 5 days) was faster than the later stage, and reductions in the first five days were more than 50% for most genes.
Topics: Anaerobiosis; Bioreactors; Dairying; Drug Resistance, Microbial; Genes, Bacterial; Interspersed Repetitive Sequences; Least-Squares Analysis; Manure; Nonlinear Dynamics; RNA, Ribosomal, 16S
PubMed: 34432793
DOI: 10.1371/journal.pone.0254836