# | Rank | Similarity | Title + Abs. | Year | PMID |
|---|---|---|---|---|---|
| 0 | 1 | 2 | 3 | 4 | 5 |
| 9977 | 0 | 1.0000 | IncC conjugative plasmids and SXT/R391 elements repair double-strand breaks caused by CRISPR-Cas during conjugation. Bacteria have evolved defence mechanisms against bacteriophages. Restriction-modification systems provide innate immunity by degrading invading DNAs that lack proper methylation. CRISPR-Cas systems provide adaptive immunity by sampling the genome of past invaders and cutting the DNA of closely related DNA molecules. These barriers also restrict horizontal gene transfer mediated by conjugative plasmids. IncC conjugative plasmids are important contributors to the global dissemination of multidrug resistance among pathogenic bacteria infecting animals and humans. Here, we show that IncC conjugative plasmids are highly resilient to host defence systems during entry into a new host by conjugation. Using a TnSeq strategy, we uncover a conserved operon containing five genes (vcrx089-vcrx093) that confer a novel host defence evasion (hde) phenotype. We show that vcrx089-vcrx090 promote resistance against type I restriction-modification, whereas vcrx091-vcxr093 promote CRISPR-Cas evasion by repairing double-strand DNA breaks via recombination between short sequence repeats. vcrx091, vcrx092 and vcrx093 encode a single-strand binding protein, and a single-strand annealing recombinase and double-strand exonuclease related to Redβ and λExo of bacteriophage λ, respectively. Homologous genes of the integrative and conjugative element R391 also provide CRISPR-Cas evasion. Hence, the conserved hde operon considerably broadens the host range of large families of mobile elements spreading multidrug resistance. | 2020 | 32556263 |
| 9852 | 1 | 0.9988 | Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance. Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes. | 2018 | 29551265 |
| 9845 | 2 | 0.9987 | Mobile antibiotic resistance encoding elements promote their own diversity. Integrating conjugative elements (ICEs) are a class of bacterial mobile genetic elements that disseminate via conjugation and then integrate into the host cell genome. The SXT/R391 family of ICEs consists of more than 30 different elements that all share the same integration site in the host chromosome but often encode distinct properties. These elements contribute to the spread of antibiotic resistance genes in several gram-negative bacteria including Vibrio cholerae, the agent of cholera. Here, using comparative analyses of the genomes of several SXT/R391 ICEs, we found evidence that the genomes of these elements have been shaped by inter-ICE recombination. We developed a high throughput semi-quantitative method to explore the genetic determinants involved in hybrid ICE formation. Recombinant ICE formation proved to be relatively frequent, and to depend on host (recA) and ICE (s065 and s066) loci, which can independently and potentially cooperatively mediate hybrid ICE formation. s065 and s066, which are found in all SXT/R391 ICEs, are orthologues of the bacteriophage lambda Red recombination genes bet and exo, and the s065/s066 recombination system is the first Red-like recombination pathway to be described in a conjugative element. Neither ICE excision nor conjugative transfer proved to be essential for generation of hybrid ICEs. Instead conjugation facilitates the segregation of hybrids and could provide a means to select for functional recombinant ICEs containing novel combinations of genes conferring resistance to antibiotics. Thus, ICEs promote their own diversity and can yield novel mobile elements capable of disseminating new combinations of antibiotic resistance genes. | 2009 | 20019796 |
| 9233 | 3 | 0.9987 | The CRISPR/Cas bacterial immune system cleaves bacteriophage and plasmid DNA. Bacteria and Archaea have developed several defence strategies against foreign nucleic acids such as viral genomes and plasmids. Among them, clustered regularly interspaced short palindromic repeats (CRISPR) loci together with cas (CRISPR-associated) genes form the CRISPR/Cas immune system, which involves partially palindromic repeats separated by short stretches of DNA called spacers, acquired from extrachromosomal elements. It was recently demonstrated that these variable loci can incorporate spacers from infecting bacteriophages and then provide immunity against subsequent bacteriophage infections in a sequence-specific manner. Here we show that the Streptococcus thermophilus CRISPR1/Cas system can also naturally acquire spacers from a self-replicating plasmid containing an antibiotic-resistance gene, leading to plasmid loss. Acquired spacers that match antibiotic-resistance genes provide a novel means to naturally select bacteria that cannot uptake and disseminate such genes. We also provide in vivo evidence that the CRISPR1/Cas system specifically cleaves plasmid and bacteriophage double-stranded DNA within the proto-spacer, at specific sites. Our data show that the CRISPR/Cas immune system is remarkably adapted to cleave invading DNA rapidly and has the potential for exploitation to generate safer microbial strains. | 2010 | 21048762 |
| 9856 | 4 | 0.9987 | The extended regulatory networks of SXT/R391 integrative and conjugative elements and IncA/C conjugative plasmids. Nowadays, healthcare systems are challenged by a major worldwide drug resistance crisis caused by the massive and rapid dissemination of antibiotic resistance genes and associated emergence of multidrug resistant pathogenic bacteria, in both clinical and environmental settings. Conjugation is the main driving force of gene transfer among microorganisms. This mechanism of horizontal gene transfer mediates the translocation of large DNA fragments between two bacterial cells in direct contact. Integrative and conjugative elements (ICEs) of the SXT/R391 family (SRIs) and IncA/C conjugative plasmids (ACPs) are responsible for the dissemination of a broad spectrum of antibiotic resistance genes among diverse species of Enterobacteriaceae and Vibrionaceae. The biology, diversity, prevalence and distribution of these two families of conjugative elements have been the subject of extensive studies for the past 15 years. Recently, the transcriptional regulators that govern their dissemination through the expression of ICE- or plasmid-encoded transfer genes have been described. Unrelated repressors control the activation of conjugation by preventing the expression of two related master activator complexes in both types of elements, i.e., SetCD in SXT/R391 ICEs and AcaCD in IncA/C plasmids. Finally, in addition to activating ICE- or plasmid-borne genes, these master activators have been shown to specifically activate phylogenetically unrelated mobilizable genomic islands (MGIs) that also disseminate antibiotic resistance genes and other adaptive traits among a plethora of pathogens such as Vibrio cholerae and Salmonella enterica. | 2015 | 26347724 |
| 9848 | 5 | 0.9987 | Cargo Genes of Tn7-Like Transposons Comprise an Enormous Diversity of Defense Systems, Mobile Genetic Elements, and Antibiotic Resistance Genes. Transposition is a major mechanism of horizontal gene mobility in prokaryotes. However, exploration of the genes mobilized by transposons (cargo) is hampered by the difficulty in delineating integrated transposons from their surrounding genetic context. Here, we present a computational approach that allowed us to identify the boundaries of 6,549 Tn7-like transposons. We found that 96% of these transposons carry at least one cargo gene. Delineation of distinct communities in a gene-sharing network demonstrates how transposons function as a conduit of genes between phylogenetically distant hosts. Comparative analysis of the cargo genes reveals significant enrichment of mobile genetic elements (MGEs) nested within Tn7-like transposons, such as insertion sequences and toxin-antitoxin modules, and of genes involved in recombination, anti-MGE defense, and antibiotic resistance. More unexpectedly, cargo also includes genes encoding central carbon metabolism enzymes. Twenty-two Tn7-like transposons carry both an anti-MGE defense system and antibiotic resistance genes, illustrating how bacteria can overcome these combined pressures upon acquisition of a single transposon. This work substantially expands the distribution of Tn7-like transposons, defines their evolutionary relationships, and provides a large-scale functional classification of prokaryotic genes mobilized by transposition. IMPORTANCE Transposons are major vehicles of horizontal gene transfer that, in addition to genes directly involved in transposition, carry cargo genes. However, characterization of these genes is hampered by the difficulty of identification of transposon boundaries. We developed a computational approach for detecting transposon ends and applied it to perform a comprehensive census of the cargo genes of Tn7-like transposons, a large class of bacterial mobile genetic elements (MGE), many of which employ a unique, CRISPR-mediated mechanism of site-specific transposition. The cargo genes encompass a striking diversity of MGE, defense, and antibiotic resistance systems. Unexpectedly, we also identified cargo genes encoding metabolic enzymes. Thus, Tn7-like transposons mobilize a vast repertoire of genes that can have multiple effects on the host bacteria. | 2021 | 34872347 |
| 9833 | 6 | 0.9987 | Evolution of satellite plasmids can prolong the maintenance of newly acquired accessory genes in bacteria. Transmissible plasmids spread genes encoding antibiotic resistance and other traits to new bacterial species. Here we report that laboratory populations of Escherichia coli with a newly acquired IncQ plasmid often evolve 'satellite plasmids' with deletions of accessory genes and genes required for plasmid replication. Satellite plasmids are molecular parasites: their presence reduces the copy number of the full-length plasmid on which they rely for their continued replication. Cells with satellite plasmids gain an immediate fitness advantage from reducing burdensome expression of accessory genes. Yet, they maintain copies of these genes and the complete plasmid, which potentially enables them to benefit from and transmit the traits they encode in the future. Evolution of satellite plasmids is transient. Cells that entirely lose accessory gene function or plasmid mobility dominate in the long run. Satellite plasmids also evolve in Snodgrassella alvi colonizing the honey bee gut, suggesting that this mechanism may broadly contribute to the importance of IncQ plasmids as agents of bacterial gene transfer in nature. | 2019 | 31863068 |
| 9819 | 7 | 0.9987 | Site-specific recombination and shuffling of resistance genes in transposon Tn21. Many multidrug-resistant transposons found in natural isolates of Gram-negative bacteria are close relatives of Tn21. Thus, the Tn21 subgroup of the Tn3 family of transposable elements is the most successful homogeneous group in acquiring resistance to newly introduced antibiotics. This paper summarizes the mode of acquisition of resistance genes by these elements. | 1991 | 1660178 |
| 9234 | 8 | 0.9987 | CRISPR provides acquired resistance against viruses in prokaryotes. Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity. | 2007 | 17379808 |
| 9855 | 9 | 0.9986 | Conjugative IncC Plasmid Entry Triggers the SOS Response and Promotes Effective Transfer of the Integrative Antibiotic Resistance Element SGI1. The broad-host-range IncC plasmid family and the integrative mobilizable Salmonella genomic island 1 (SGI1) and its derivatives enable the spread of medically important antibiotic resistance genes among Gram-negative pathogens. Although several aspects of the complex functional interactions between IncC plasmids and SGI1 have been recently deciphered regarding their conjugative transfer and incompatibility, the biological signal resulting in the hijacking of the conjugative plasmid by the integrative mobilizable element remains unknown. Here, we demonstrate that the conjugative entry of IncC/IncA plasmids is detected at an early stage by SGI1 through the transient activation of the SOS response, which induces the expression of the SGI1 master activators SgaDC, shown to play a crucial role in the complex biology between SGI1 and IncC plasmids. Besides, we developed an original tripartite conjugation approach to directly monitor SGI1 mobilization in a time-dependent manner following conjugative entry of IncC plasmids. Finally, we propose an updated biological model of the conjugative mobilization of the chromosomal resistance element SGI1 by IncC plasmids. IMPORTANCE Antimicrobial resistance has become a major public health issue, particularly with the increase of multidrug resistance (MDR) in both animal and human pathogenic bacteria and with the emergence of resistance to medically important antibiotics. The spread between bacteria of successful mobile genetic elements, such as conjugative plasmids and integrative elements conferring multidrug resistance, is the main driving force in the dissemination of acquired antibiotic resistances among Gram-negative bacteria. Broad-host-range IncC plasmids and their integrative mobilizable SGI1 counterparts contribute to the spread of critically important resistance genes (e.g., extended-spectrum β-lactamases [ESBLs] and carbapenemases). A better knowledge of the complex biology of these broad-host-range mobile elements will help us to understand the dissemination of antimicrobial resistance genes that occurred across Gammaproteobacteria borders. | 2023 | 36472437 |
| 9851 | 10 | 0.9986 | The potential of integrons and connected programmed rearrangements for mediating horizontal gene transfer. Site-specific recombination of integrons, mediates transfer of single genes in small genomes and plasmids. Recent data suggest that new genes are recruited to the cassettes--the units moved by integrons. Integrons are resident in a class of transposons with pronounced target selectivity for resolution loci in broad host range plasmids. A resulting network of programmed transfer routes, with potential offshoots reaching into eukaryotic cells, may channel genes to unexpectedly remote organisms. It has previously been observed that the conjugation apparatus of the broad host range plasmid R751 (IncP) which contains transposon Tn5090 harbouring an integron, promotes horizontal genetic transfer between bacteria and yeast. Furthermore, it is well known and fundamental for widely used gene replacement technologies, that site-specific recombination systems (e.g. Cre-lox of bacteriophage P1) related to the integrons are functional in higher eukaryotes. It seems very clear that integrons and associated programmed transfer mechanisms have high significance for the dissemination of antibiotic resistance genes in bacteria whereas further studies are needed to assess their importance for spreading of arbitrary genes in a wider range of host systems. | 1998 | 9850680 |
| 9830 | 11 | 0.9986 | Mechanisms of Conjugative Transfer and Type IV Secretion-Mediated Effector Transport in Gram-Positive Bacteria. Conjugative DNA transfer is the most important means to transfer antibiotic resistance genes and virulence determinants encoded by plasmids, integrative conjugative elements (ICE), and pathogenicity islands among bacteria. In gram-positive bacteria, there exist two types of conjugative systems, (i) type IV secretion system (T4SS)-dependent ones, like those encoded by the Enterococcus, Streptococcus, Staphylococcus, Bacillus, and Clostridia mobile genetic elements and (ii) T4SS-independent ones, as those found on Streptomyces plasmids. Interestingly, very recently, on the Streptococcus suis genome, the first gram-positive T4SS not only involved in conjugative DNA transfer but also in effector translocation to the host was detected. Although no T4SS core complex structure from gram-positive bacteria is available, several structures from T4SS protein key factors from Enterococcus and Clostridia plasmids have been solved. In this chapter, we summarize the current knowledge on the molecular mechanisms and structure-function relationships of the diverse conjugation machineries and emerging research needs focused on combatting infections and spread of multiple resistant gram-positive pathogens. | 2017 | 29536357 |
| 9818 | 12 | 0.9986 | ISCR elements: novel gene-capturing systems of the 21st century? "Common regions" (CRs), such as Orf513, are being increasingly linked to mega-antibiotic-resistant regions. While their overall nucleotide sequences show little identity to other mobile elements, amino acid alignments indicate that they possess the key motifs of IS91-like elements, which have been linked to the mobility ent plasmids in pathogenic Escherichia coli. Further inspection reveals that they possess an IS91-like origin of replication and termination sites (terIS), and therefore CRs probably transpose via a rolling-circle replication mechanism. Accordingly, in this review we have renamed CRs as ISCRs to give a more accurate reflection of their functional properties. The genetic context surrounding ISCRs indicates that they can procure 5' sequences via misreading of the cognate terIS, i.e., "unchecked transposition." Clinically, the most worrying aspect of ISCRs is that they are increasingly being linked with more potent examples of resistance, i.e., metallo-beta-lactamases in Pseudomonas aeruginosa and co-trimoxazole resistance in Stenotrophomonas maltophilia. Furthermore, if ISCR elements do move via "unchecked RC transposition," as has been speculated for ISCR1, then this mechanism provides antibiotic resistance genes with a highly mobile genetic vehicle that could greatly exceed the effects of previously reported mobile genetic mechanisms. It has been hypothesized that bacteria will surprise us by extending their "genetic construction kit" to procure and evince additional DNA and, therefore, antibiotic resistance genes. It appears that ISCR elements have now firmly established themselves within that regimen. | 2006 | 16760305 |
| 9829 | 13 | 0.9986 | Promiscuous transfer of drug resistance in gram-negative bacteria. Bacterial conjugation is a major mechanism for the spread of antibiotic-resistance genes in pathogenic organisms. In gram-negative bacteria, broad-host-range drug-resistance plasmids mediate genetic exchange between many unrelated species. The mechanism of conjugation encoded by the broad-host-range IncP plasmid RK2 has been studied in detail. The location and sequence of the transfer origin of RK2 has been determined. Several barriers limit plasmid transfer between unrelated bacteria: interactions at the cell surface may prevent effective mating contact, restriction systems may degrade foreign DNA, or the plasmid may not replicate in the new host. RK2 has evolved specific mechanisms by which it overcomes these barriers; this plasmid can mediate the transfer of resistance to most gram-negative bacteria. | 1984 | 6143782 |
| 9853 | 14 | 0.9986 | The master activator of IncA/C conjugative plasmids stimulates genomic islands and multidrug resistance dissemination. Dissemination of antibiotic resistance genes occurs mostly by conjugation, which mediates DNA transfer between cells in direct contact. Conjugative plasmids of the IncA/C incompatibility group have become a substantial threat due to their broad host-range, the extended spectrum of antimicrobial resistance they confer, their prevalence in enteric bacteria and their very efficient spread by conjugation. However, their biology remains largely unexplored. Using the IncA/C conjugative plasmid pVCR94ΔX as a prototype, we have investigated the regulatory circuitry that governs IncA/C plasmids dissemination and found that the transcriptional activator complex AcaCD is essential for the expression of plasmid transfer genes. Using chromatin immunoprecipitation coupled with exonuclease digestion (ChIP-exo) and RNA sequencing (RNA-seq) approaches, we have identified the sequences recognized by AcaCD and characterized the AcaCD regulon. Data mining using the DNA motif recognized by AcaCD revealed potential AcaCD-binding sites upstream of genes involved in the intracellular mobility functions (recombination directionality factor and mobilization genes) in two widespread classes of genomic islands (GIs) phylogenetically unrelated to IncA/C plasmids. The first class, SGI1, confers and propagates multidrug resistance in Salmonella enterica and Proteus mirabilis, whereas MGIVmi1 in Vibrio mimicus belongs to a previously uncharacterized class of GIs. We have demonstrated that through expression of AcaCD, IncA/C plasmids specifically trigger the excision and mobilization of the GIs at high frequencies. This study provides new evidence of the considerable impact of IncA/C plasmids on bacterial genome plasticity through their own mobility and the mobilization of genomic islands. | 2014 | 25340549 |
| 9817 | 15 | 0.9986 | Common regions e.g. orf513 and antibiotic resistance: IS91-like elements evolving complex class 1 integrons. The ability of bacteria to procure, sometimes rearrange, and evince acquired DNA continues to impress us-even more so if this genetic plasticity involves the sequestering of antibiotic resistance genes. The acquisition of genes in bacteria is often facilitated by transposons, integrons and archetype insertion elements. Recently however, a new element, 'orf513', has been increasingly associated with class 1 integrons. Moreover, these 'complex' class 1 integrons can potentially mediate resistance to chloramphenicol, trimethoprim, aminoglycosides and tetracycline and may carry a range of beta-lactamase genes as well as the qnrA gene. Elements such as 'orf513' demonstrate IS91-like characteristics and will mobilize adjacent DNA via a process called rolling circle replication, and thus we have renamed them 'insertion sequence CRs' (ISCRs) to appropriately reflect their structure-function properties. In this article, we provide a brief description of these new and clinically important mobile elements, and how they are able to mobilize antibiotic resistance genes. | 2006 | 16751201 |
| 9306 | 16 | 0.9986 | Establishment Genes Present on pLS20 Family of Conjugative Plasmids Are Regulated in Two Different Ways. During conjugation, a conjugative DNA element is transferred from a donor to a recipient cell via a connecting channel. Conjugation has clinical relevance because it is the major route for spreading antibiotic resistance and virulence genes. The conjugation process can be divided into different steps. The initial steps carried out in the donor cell culminate in the transfer of a single DNA strand (ssDNA) of the conjugative element into the recipient cell. However, stable settlement of the conjugative element in the new host requires at least two additional events: conversion of the transferred ssDNA into double-stranded DNA and inhibition of the hosts' defence mechanisms to prevent degradation of the transferred DNA. The genes involved in this late step are historically referred to as establishment genes. The defence mechanisms of the host must be inactivated rapidly and-importantly-transiently, because prolonged inactivation would make the cell vulnerable to the attack of other foreign DNA, such as those of phages. Therefore, expression of the establishment genes in the recipient cell has to be rapid but transient. Here, we studied regulation of the establishment genes present on the four clades of the pLS20 family of conjugative plasmids harboured by different Bacillus species. Evidence is presented that two fundamentally different mechanisms regulate the establishment genes present on these plasmids. Identification of the regulatory sequences were critical in revealing the establishment regulons. Remarkably, whereas the conjugation genes involved in the early steps of the conjugation process are conserved and are located in a single large operon, the establishment genes are highly variable and organised in multiple operons. We propose that the mosaical distribution of establishment genes in multiple operons is directly related to the variability of defence genes encoded by the host bacterial chromosomes. | 2021 | 34946067 |
| 9846 | 17 | 0.9986 | Integrative Conjugative Elements (ICEs) of the SXT/R391 family drive adaptation and evolution in γ-Proteobacteria. Integrative Conjugative Elements (ICEs) are mosaics containing functional modules allowing maintenance by site-specific integration and excision into and from the host genome and conjugative transfer to a specific host range. Many ICEs encode a range of adaptive functions that aid bacterial survival and evolution in a range of niches. ICEs from the SXT/R391 family are found in γ-Proteobacteria. Over 100 members have undergone epidemiological and molecular characterization allowing insight into their diversity and function. Comparative analysis of SXT/R391 elements from a wide geographic distribution has revealed conservation of key functions, and the accumulation and evolution of adaptive genes. This evolution is associated with gene acquisition in conserved hotspots and variable regions within the SXT/R391 ICEs catalysed via element-encoded recombinases. The elements can carry IS elements and transposons, and a mutagenic DNA polymerase, PolV, which are associated with their evolution. SXT/R391 ICEs isolated from different niches appear to have retained adaptive functions related to that specific niche; phage resistance determinants in ICEs carried by wastewater bacteria, antibiotic resistance determinants in clinical isolates and metal resistance determinants in bacteria recovered from polluted environments/ocean sediments. Many genes found in the element hotspots are undetermined and have few homologs in the nucleotide databases. | 2024 | 36634159 |
| 9822 | 18 | 0.9986 | Molecular mechanisms for transposition of drug-resistance genes and other movable genetic elements. Transposition is proposed to be responsible for the rapid evolution of multiply drug-resistant bacterial strains. Transposons, which carry the genes encoding drug resistance, are linear pieces of DNA that range in size from 2.5 to 23 kilobase pairs and always contain at their ends nucleotide sequences repeated in inverse order. In some transposons the terminal inverted repeat sequences are capable of independent movement and are called insertion sequences. Transposons carry a gene that encodes transposase(s), the enzyme(s) responsible for recombination of the transposon into another DNA molecule. Studies on transposable genetic elements in bacteria have not only given insight into the spread of antibiotic resistance but also into the process of DNA movement. | 1987 | 3035697 |
| 9235 | 19 | 0.9986 | Investigating the Genomic Background of CRISPR-Cas Genomes for CRISPR-Based Antimicrobials. CRISPR-Cas systems are an adaptive immunity that protects prokaryotes against foreign genetic elements. Genetic templates acquired during past infection events enable DNA-interacting enzymes to recognize foreign DNA for destruction. Due to the programmability and specificity of these genetic templates, CRISPR-Cas systems are potential alternative antibiotics that can be engineered to self-target antimicrobial resistance genes on the chromosome or plasmid. However, several fundamental questions remain to repurpose these tools against drug-resistant bacteria. For endogenous CRISPR-Cas self-targeting, antimicrobial resistance genes and functional CRISPR-Cas systems have to co-occur in the target cell. Furthermore, these tools have to outplay DNA repair pathways that respond to the nuclease activities of Cas proteins, even for exogenous CRISPR-Cas delivery. Here, we conduct a comprehensive survey of CRISPR-Cas genomes. First, we address the co-occurrence of CRISPR-Cas systems and antimicrobial resistance genes in the CRISPR-Cas genomes. We show that the average number of these genes varies greatly by the CRISPR-Cas type, and some CRISPR-Cas types (IE and IIIA) have over 20 genes per genome. Next, we investigate the DNA repair pathways of these CRISPR-Cas genomes, revealing that the diversity and frequency of these pathways differ by the CRISPR-Cas type. The interplay between CRISPR-Cas systems and DNA repair pathways is essential for the acquisition of new spacers in CRISPR arrays. We conduct simulation studies to demonstrate that the efficiency of these DNA repair pathways may be inferred from the time-series patterns in the RNA structure of CRISPR repeats. This bioinformatic survey of CRISPR-Cas genomes elucidates the necessity to consider multifaceted interactions between different genes and systems, to design effective CRISPR-based antimicrobials that can specifically target drug-resistant bacteria in natural microbial communities. | 2022 | 35692726 |