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IME-encoded factors that contribute to IME maintenance in the cell during cell division: I Replication factors allowing rolling circle replication (RCR) or theta replication; II, toxin-antitoxin systems; III, partition protein ParB.
Source publication
Conjugation is a key mechanism of bacterial evolution that involves mobile genetic elements. Recent findings indicated that the main actors of conjugative transfer are not the well-known conjugative or mobilizable plasmids but are the integrated elements. This paper reviews current knowledge on “integrative and mobilizable elements” (IMEs) that hav...
Contexts in source publication
Context 1
... the maintenance of excised ICEs TnGBS1 and TnGBS2 from S. agalactiae, involves replication via two different theta dedicated replication systems, independent of the conjugative relaxase [71]. In the same way, although the replication of excised IMEs has never been studied, it should be noticed that, besides their relaxase, various IMEs encode proteins that are related to factors involved in the initiation of the replication of plasmids or phages and could be involved in maintenance of the IME after excision (Figure 2). These proteins are homologous to (i) theta replication initiators belonging to the Rep_3 superfamily (SGI1 and BcenGI2); (ii) replisome organizers and DnaC that are involved in initiation of the theta replication of various prophages (Tn6104 and various IMEs from Streptococci); (iii) RepA and RepC involved in theta plasmid replication (GISul2, IncP islands, tet(O) fragment); or (iv) RCR initiators belonging to the Rep_Trans family (various IMEs from Streptococci such as IMESag-rpsI and IME_Sga2069_rpmE) (Table 1). ...
Context 2
... proteins are homologous to (i) theta replication initiators belonging to the Rep_3 superfamily (SGI1 and BcenGI2); (ii) replisome organizers and DnaC that are involved in initiation of the theta replication of various prophages (Tn6104 and various IMEs from Streptococci); (iii) RepA and RepC involved in theta plasmid replication (GISul2, IncP islands, tet(O) fragment); or (iv) RCR initiators belonging to the Rep_Trans family (various IMEs from Streptococci such as IMESag-rpsI and IME_Sga2069_rpmE) (Table 1). Furthermore, many IMEs from Streptococci (Table 1, [26]), which do not encode such replication proteins, encode non-canonical putative relaxases that might be used for both conjugative transfer and maintenance of the excised element ( Figure 2). Indeed, these non- canonical relaxases are related to RCR initiators that are involved in the replication of many small plasmids from Firmicutes (Rep_Trans/MobT, Rep_2) or of phages (Viral_Rep, PHA00330). ...
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... belonging to the SXT/R391 family further reduce the chance of losing their excised form by deploying active partition systems related to those of plasmids [74]. It could also be the case of some IMEs from Streptococci, such as the tet(O) fragment, that encode proteins related to ParB, a protein involved in the active partition of plasmids (Table 1 and Figure 2). ICEs often encode addiction systems such as toxin-antitoxin (TA) [21] or type II restriction-modification (RM) [75] that can trigger post-segregational killing of daughter cells that have lost the element [76]. ...
Context 4
... often encode addiction systems such as toxin-antitoxin (TA) [21] or type II restriction-modification (RM) [75] that can trigger post-segregational killing of daughter cells that have lost the element [76]. Sequence analyses revealed complete TA or type II RM systems that possibly act as addiction system in various IMEs from Proteobacteria, Firmicutes and Actinobacteria (Table 1 and Figure 2). Only one, SGI1 from S. enterica, was recently studied in this perspective. ...
Similar publications
Group II introns are self-splicing ribozymes and mobile genetic elements. Splicing is required for both expression of the interrupted host gene and intron retromobility. For the pRS01 plasmid-encoded Lactococcus lactis group II intron, Ll.LtrB, splicing enables expression of the intron's host relaxase protein. Relaxase, in turn, initiates horizonta...
Citations
... 11,12 Conjugative plasmids encode products for facilitating conjugation, including relaxase (induction of DNA strand breaks and rejoining), type IV secretion systems (transmembrane channel linking donor and recipient bacteria and DNA transfer), oriT (origin of transfer), and coupling proteins (intracellular machinery to link the secretion system). 13 IMEs typically utilize conjugation mechanisms encoded by other MGEs to achieve transfer and integration 14 while ICEs mainly use tyrosine/serine recombinases or DDE transposases for chromosomal integration and excision. 15 In previous study, a number of novel MGEs were identified in P. aeruginosa in China, such as the novel Inc groups: Inc p60512−IMP and Inc pPA7790 ; 16 Tn6852-related IMEs carrying bla PER-1 and bla CARB-2 : Tn6853; 17 Tn6417-related ICEs carrying bla VIM-1 : Tn6953; 18 and Multiple Tn1403-related transposons carrying different class 1 integrons: Tn6847, Tn6849, Tn7454, Tn7484, etc. 16,17,19 Multiple types of novel MGEs are frequently identified in China, which pose unknown challenges to the containment of bacterial resistance. ...
Purpose
Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.
Methods
Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.
Results
The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn501-related unit transposons, two Tn1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.
Conclusion
The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.
... In addition, our findings suggest that the presence of ARs in ICEs/ IMEs may contribute to the spread of antibiotic resistance among bacterial populations. Overall, our study emphasizes the need for a more comprehensive approach to address antibiotic resistance, considering the role of ICEs/IMEs [31]. ...
Persistent nasal carriage has been associated with Staphylococcus aureus infection. Previous S. aureus studies in Asia have primarily focused on clinical patients, providing limited information on persistent nasal carriage among the general adult population.
This study examined 143 healthy adults in a community in Jiangsu, China. Nasal swab samples were collected 10 times. The colonization status was identified using SPA typing. We also determined antimicrobial susceptibility, genotype, and genomic characteristics of S. aureus.
The prevalence of S. aureus nasal carriage among the community individuals was on average 16.78%. The carriage rates of methicillin-resistant S. aureus and multidrug-resistant S. aureus were 6.29% and 7.69%, respectively. We identified 8.39% persistent carriers, 39.16% intermittent carriers, and 52.45% noncarriers. Furthermore, family members displayed concordance in terms of genotype and genomic characteristics.
Persistent nasal sampling captured intermittent carriers that were missed during short-term sampling, thus highlighting the necessity for regular community testing. SPA typing can serve as a rapid method for determining S. aureus colonization. The potential for intrafamilial transmission of S. aureus is evident, with persistent carriers being the most probable source of infection.
... Because transfer and carriage of MGEs have been usually assumed to be costly, they are open considered geneEc parasites of bacteria (86). Likewise, since the mobilizaeon of HGEs may be costly to other MGEs (helpers) which may be costly to the bacterial host, they could be considered as geneEc hyper-parasites (i.e., parasites of the parasites) (87,88). But is this really the case? ...
... One intriguing property common to all types of HGEs is that they tend to be much smaller than those of their helpers. For example, conjugaeve elements have a median size more than five emes larger than the mobilizable elements (43,88), even if a few excepeons have been described (123). The genomes of phage satellites are also typically much smaller (6-18Kbs) (10,17) than those of their helpers (dsDNA, usually >> 25kb). ...
Mobile genetic elements shape microbial gene repertoires and population dynamics, but their mechanisms of horizontal transmission are often unknown. Recent results reveal that many, possibly most, bacterial mobile genetic elements require helper elements to transfer between (or within) genomes. We refer to these non-autonomous, albeit mobile, elements as Hitcher Genetic Elements (hitchers or HGEs). They could constitute a large fraction of pathogenicity and resistance genomic islands, whose mechanisms of transfer have remained enigmatic for decades. Together with their helper elements and their bacterial hosts, hitchers are in tripartite networks of interactions that evolve within a parasitism-mutualism continuum, with advantages and costs to each party. The emerging view of microbial genomes as networks of interacting mobile genetic elements brings to the fore many mysteries. Which elements are being moved, by whom, and how? How often are hitchers costly hyper-parasites or instead beneficial mutualists to their helpers and to the bacterial hosts? What is the evolutionary origin of hitchers? Are there key advantages associated with hitchers' lifestyle that justify their unexpected abundance across genomes? Or is their frequency largely the result of selfish spread across communities? Understanding the principles, origin, mechanisms, and impact of Hitcher Genetic Elements will lead to key insights in bacterial ecology and evolution.
... IMEs also encode their own excision and integration in the bacterial chromosome but rely on the conjugative apparatus of conjugative elements to transfer by conjugation. These mobile elements have been less studied than ICEs because they are more difficult to identify in bacterial genomes, particularly in streptococci since they are frequently found as composite elements (accretion with other MGEs in tandem or integrated inside) [21,22]. ...
... IMEs can be classified according to the family of their relaxase [22]. The most prevalent family of IMEs detected in the genomes harbours a relaxase with a PF02486 domain (MobT family, n=72) (Fig. 6). ...
Streptococcus suis is a leading cause of infection in pigs, causing extensive economic losses. In addition, it can also infect wild fauna, and can be responsible for severe infections in humans. Increasing antimicrobial resistance (AMR) has been described in S. suis worldwide and most of the AMR genes are carried by mobile genetic elements (MGEs). This contributes to their dissemination by horizontal gene transfer. A collection of 102 strains isolated from humans, pigs and wild boars in France was subjected to whole genome sequencing in order to: (i) study their genetic diversity, (ii) evaluate their content in virulence-associated genes, (iii) decipher the mechanisms responsible for their AMR and their association with MGEs, and (iv) study their ability to acquire extracellular DNA by natural transformation. Analysis by hierarchical clustering on principal components identified a few virulence-associated factors that distinguish invasive CC1 strains from the other strains. A plethora of AMR genes ( n =217) was found in the genomes. Apart from the frequently reported erm (B) and tet (O) genes, more recently described AMR genes were identified [ vga (F)/ sprA , vat (D)]. Modifications in PBPs/MraY and GyrA/ParC were detected in the penicillin- and fluoroquinolone-resistant isolates respectively. New AMR gene–MGE associations were detected. The majority of the strains have the full set of genes required for competence, i.e for the acquisition of extracellular DNA (that could carry AMR genes) by natural transformation. Hence the risk of dissemination of these AMR genes should not be neglected.
... Although IMEs can integrate into host chromosomes, they lack the genes necessary for conjugation and, thus, depend on the presence of other conjugative elements, including conjugative plasmids or ICEs, for mobilisation and transfer to other bacterial cells. CIMEs are flanked by recombination sites (attL and attR), which are recognised by the integrase of an ICE or IME with which they are associated, but CIMEs lack the genes necessary for conjugation or recombination (Bellanger et al., 2014;Guédon et al., 2017). Like plasmids, these elements can carry genes encoding virulence factors and metabolic traits and ARGs, among other functions. ...
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.
... In the mobilization module orf3, orf4 and orf5 encode FtsK homologous proteins and a relaxase, respectively, which probably constitute the relaxosome [51]. The integration/ excision module contains orf7 and orf8 coding for a putative excisionase and for a site-specific integrase that belongs to the family of tyrosine recombinases, as reported for many IMEs [52]. IMEs integrate into the bacterial genome and are capable of intracellular transposition to a new genomic site or intercellular transposition to a new host using in trans the conjugation machinery of a helper ICE or conjugative plasmid [40,53]. ...
Lactobacillus crispatus is a member of the vaginal and gastrointestinal human microbiota. Here we determined the complete genome sequence of the probiotic strain M247 combining Nanopore and Illumina technologies. The M247 genome is organized in one circular chromosome of 2 336 109 bp, with a GC content of 37.04 % and 2303 ORFs, of which 1962 could be annotated. Analysis of the M247 mobilome, which accounts for 14 % of the whole genome, revealed the presence of: (i) Tn 7088 , a novel 14 105 bp long integrative and mobilizable element (IME) containing 16 ORFs; (ii) ΦM247, a novel 42 510 bp long siphovirus prophage containing 52 ORFs; (iii) three clustered regularly interspaced short palindromic repeats (CRISPRs); and (iv) 226 insertion sequences (ISs) belonging to 14 different families. Tn 7088 has a modular organization including a mobilization module encoding FtsK homologous proteins and a relaxase, an integration/excision module coding for an integrase and an excisionase, and an adaptation module coding for a class I bacteriocin and homologous to the listeriolysin S ( lls ) locus of Listeria monocytogenes . Genome-wide homology search analysis showed the presence of Tn 7088 -like elements in 12 out of 23 L . crispatus complete public genomes. Mobilization and integration/excision modules are essentially conserved, while the adaptation module is variable since it is the target site for the integration of different ISs. Prophage ΦM247 contains genes for phage structural proteins, DNA replication and packaging, lysogenic and lytic cycles. ΦM247-like prophages are present in seven L . crispatus complete genomes, with sequence variability mainly due to the integration of ISs. PCR and sequencing showed that the Tn 7088 IME excises from the M247 chromosome producing a circular form at a concentration of 4.32×10 ⁻⁵ copies per chromosome, and reconstitution of the Tn 7088 chromosomal target site occurred at 6.65×10 ⁻⁴ copies per chromosome. The ΦM247 prophage produces an excised form and a reconstituted target site at a level of 3.90×10 ⁻⁵ and 2.48×10 ⁻⁵ copies per chromosome, respectively. This study identified two novel genetic elements in L. crispatus . Tn 7088 represents the first example of an IME carrying a biosynthetic gene cluster for a class I bacteriocin in L. crispatus .
... However, IME2287 lacks the conjugation module, often consisting of a relaxase, a coupling protein, and a mating pair formation system [61]. We also identified IR and DR flanking IME2287, suggesting that this genetic element is likely a mobilizable transposon or a non-canonical IME [62]. The distinction between mobilizable transposons and IMEs is unclear and is considered irrelevant for some [62]. ...
... We also identified IR and DR flanking IME2287, suggesting that this genetic element is likely a mobilizable transposon or a non-canonical IME [62]. The distinction between mobilizable transposons and IMEs is unclear and is considered irrelevant for some [62]. Various non-canonical IMEs (that do not encode any relaxase) have been identified in the Firmicutes and Proteobacteria phyla, sometimes with several copies integrated in tandem, like in the case of IME2287 [63]. ...
Decades of antimicrobial overuse to treat respiratory disease in foals have promoted the emergence and spread of zoonotic multidrug-resistant (MDR) Rhodococcus equi worldwide. Three main R. equi MDR clonal populations—2287, G2106, and G2017—have been identified so far. However, only clones 2287 and G2016 have been isolated from sick animals, with clone 2287 being the main MDR R. equi recovered. The genetic mechanisms that make this MDR clone superior to the others at infecting foals are still unknown. Here, we performed a deep genetic characterization of the accessory genomes of 207 R. equi isolates, and we describe IME2287, a novel genetic element in the accessory genome of clone 2287, potentially involved in the maintenance and spread of this MDR population over time. IME2287 is a putative self-replicative integrative mobilizable element (IME) carrying a DNA replication and partitioning operon and genes encoding its excision and integration from the R. equi genome via a serine recombinase. Additionally, IME2287 encodes a protein containing a Toll/interleukin-1 receptor (TIR) domain that may inhibit TLR-mediated NF-kB signaling in the host and a toxin–antitoxin (TA) system, whose orthologs have been associated with antibiotic resistance/tolerance, virulence, pathogenicity islands, bacterial persistence, and pathogen trafficking. This new set of genes may explain the success of clone 2287 over the other MDR R. equi clones.
... They are frequently involved in the transfer and dissemination of antibiotic-resistance genes, serving as essential vehicles for the spread of antibiotic resistance [9,10]. Integrative and mobilizable elements (IMEs) are a class of MGEs that are often located on the chromosome [11]. IMEs are distinguished by their capacity to integrate and exploit the conjugative apparatus of unrelated co-resident conjugative elements to promote their transfer [11]. ...
... Integrative and mobilizable elements (IMEs) are a class of MGEs that are often located on the chromosome [11]. IMEs are distinguished by their capacity to integrate and exploit the conjugative apparatus of unrelated co-resident conjugative elements to promote their transfer [11]. IMEs are typically comprised of several critical components, including int (integrase), rlx (relaxase), oriT (origin of conjugative replication), and attL/attR (attachment site at the left/right end of the IME). ...
... IMEs are typically comprised of several critical components, including int (integrase), rlx (relaxase), oriT (origin of conjugative replication), and attL/attR (attachment site at the left/right end of the IME). Previous research has demonstrated that IMEs are highly diverse and widely distributed [11]. IMEs have been shown to play a crucial role in the acquisition and accumulation of antibiotic resistance genes, thereby contributing to the emergence of novel genetic environments for antibiotic resistance [12,13]. ...
The emergence of antibiotic-resistant Aeromonas strains in clinical settings has presented an escalating burden on human and public health. The dissemination of antibiotic resistance in Aeromonas is predominantly facilitated by chromosome-borne accessory genetic elements, although the existing literature on this subject remains limited. Hence, the primary objective of this study is to comprehensively investigate the genomic characteristics of chromosome-borne accessory genetic elements in Aeromonas. Moreover, the study aims to uncover novel genetic environments associated with antibiotic resistance on these elements. Aeromonas were screened from nonduplicated strains collected from two tertiary hospitals in China. Complete sequencing and population genetics analysis were performed. BLAST analysis was employed to identify related elements. All newly identified elements were subjected to detailed sequence annotation, dissection, and comparison. We identified and newly designated 19 chromosomal elements, including 18 integrative and mobilizable elements (IMEs) that could be classified into four categories: Tn6737-related, Tn6836-related, Tn6840-related, and Tn6844a-related IMEs. Each class exhibited a distinct pattern in the types of resistance genes carried by the IMEs. Several novel antibiotic resistance genetic environments were uncovered in these elements. Notably, we report the first identification of the blaOXA-10 gene and blaVEB-1 gene in clinical A. veronii genome, the first presence of a tetA(E)–tetR(E) resistance gene environment within the backbone region in IMEs, and a new mcr-3.15 resistance gene environment. The implications of these findings are substantial, as they provide new insights into the evolution, structure, and dissemination of chromosomal-borne accessory elements.
... Typical plasmids are composed of a backbone and several variable regions, which usually carries different species and different numbers of mobilizable elements including transposons, integrons and insertion sequences (ISs). Moreover, these mobilizable elements usually carry antibiotic resistance genes; therefore, horizontal gene transfer mediated by plasmids makes a significant contribution to the dissemination of antibiotic resistance genes between different bacterial species [16]. ...
Klebsiella michiganensis is a recently emerging human pathogen causing nosocomial infections. This study aimed to characterize the complete genome sequence of a clinical Klebsiella michiganensis strain KMIB106 which exhibited extensive drug-resistance. The whole genome of the strain was sequenced using PacBio RS III systems and Illumina Nextseq 500. Annotation, transposable elements and resistance gene identification were analyzed by RAST, prokka and Plasmid Finder, respectively. According to the results, KMIB106 was resistant to multiple antimicrobials, including carbapenems, but it remained susceptible to aztreonam. The genome of KMIB106 consisted of a single chromosome and three predicted plasmids. Importantly, a novel KPC plasmid pB106-1 was found to carry the array of resistance genes in a highly different order in its variable regions, including mphA, msrE, mphE, ARR-3, addA16, sul1, dfrA27, tetD and fosA3. Plasmid pB106-2 is a typical IncFII plasmid with no resistant gene. Plasmid pB106-IMP consists of the IncN and IncX3 backbones, and two resistance genes, blaIMP-4 and blaSHV-12, were identified. Our study for the first time reported an extensively drug-resistant Klebsiella michiganensis strain recovered from a child with a respiratory infection in Southern China, which carries three mega plasmids, with pB106-1 firstly identified to carry an array of resistance genes in a distinctive order, and pB106-IMP identified as a novel IncN-IncX3 cointegrate plasmid harboring two resistance genes blaIMP-4 and blaSHV-12.
... IMEs encode the recombination module, allowing them to integrate into and excise from bacterial attachment sites. However, they carry only some sequences or genes necessary for their conjugative transfer [27]. Prophage-mediated transfer is known to occur mainly through generalized, specialized and lateral transduction [28][29][30]. ...
Prophages play important roles in the transduction of various functional traits, including virulence factors, but remain debatable in harboring and transmitting antimicrobial resistance genes (ARGs). Herein we characterize a prevalent family of prophages in Streptococcus, designated SMphages, which harbor twenty-five ARGs that collectively confer resistance to ten antimicrobial classes, including vanG-type vancomycin resistance locus and oxazolidinone resistance gene optrA. SMphages integrate into four chromosome attachment sites by utilizing three types of integration modules and undergo excision in response to phage induction. Moreover, we characterize four subtypes of Alp-related surface proteins within SMphages, the lethal effects of which are extensively validated in cell and animal models. SMphages transfer via high-frequency conjugation that is facilitated by integrative and conjugative elements from either donors or recipients. Our findings explain the widespread of SMphages and the rapid dissemination of ARGs observed in members of the Streptococcus genus.
