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Molecular Systems Biology Apr 2024Antimicrobial resistance (AMR) in bacteria is a major public health threat and conjugative plasmids play a key role in the dissemination of AMR genes among bacterial... (Review)
Review
Antimicrobial resistance (AMR) in bacteria is a major public health threat and conjugative plasmids play a key role in the dissemination of AMR genes among bacterial pathogens. Interestingly, the association between AMR plasmids and pathogens is not random and certain associations spread successfully at a global scale. The burst of genome sequencing has increased the resolution of epidemiological programs, broadening our understanding of plasmid distribution in bacterial populations. Despite the immense value of these studies, our ability to predict future plasmid-bacteria associations remains limited. Numerous empirical studies have recently reported systematic patterns in genetic interactions that enable predictability, in a phenomenon known as global epistasis. In this perspective, we argue that global epistasis patterns hold the potential to predict interactions between plasmids and bacterial genomes, thereby facilitating the prediction of future successful associations. To assess the validity of this idea, we use previously published data to identify global epistasis patterns in clinically relevant plasmid-bacteria associations. Furthermore, using simple mechanistic models of antibiotic resistance, we illustrate how global epistasis patterns may allow us to generate new hypotheses on the mechanisms associated with successful plasmid-bacteria associations. Collectively, we aim at illustrating the relevance of exploring global epistasis in the context of plasmid biology.
Topics: Anti-Bacterial Agents; Drug Resistance, Bacterial; Epistasis, Genetic; Plasmids; Genome, Bacterial; Bacteria
PubMed: 38409539
DOI: 10.1038/s44320-024-00012-1 -
The ISME Journal Oct 2021Plasmids are autonomous genetic elements that can be exchanged between microorganisms via horizontal gene transfer (HGT). Despite the central role they play in...
Plasmids are autonomous genetic elements that can be exchanged between microorganisms via horizontal gene transfer (HGT). Despite the central role they play in antibiotic resistance and modern biotechnology, our understanding of plasmids' natural ecology is limited. Recent experiments have shown that plasmids can spread even when they are a burden to the cell, suggesting that natural plasmids may exist as parasites. Here, we use mathematical modeling to explore the ecology of such parasitic plasmids. We first develop models of single plasmids and find that a plasmid's population dynamics and optimal infection strategy are strongly determined by the plasmid's HGT mechanism. We then analyze models of co-infecting plasmids and show that parasitic plasmids are prone to a "tragedy of the commons" in which runaway plasmid invasion severely reduces host fitness. We propose that this tragedy of the commons is averted by selection between competing populations and demonstrate this effect in a metapopulation model. We derive predicted distributions of unique plasmid types in genomes-comparison to the distribution of plasmids in a collection of 17,725 genomes supports a model of parasitic plasmids with positive plasmid-plasmid interactions that ameliorate plasmid fitness costs or promote the invasion of new plasmids.
Topics: Animals; Drug Resistance, Microbial; Gene Transfer, Horizontal; Parasites; Plasmids
PubMed: 33833414
DOI: 10.1038/s41396-021-00954-6 -
Molecular Biology and Evolution Mar 2019The ubiquity of plasmids in all prokaryotic phyla and habitats and their ability to transfer between cells marks them as prominent constituents of prokaryotic genomes....
The ubiquity of plasmids in all prokaryotic phyla and habitats and their ability to transfer between cells marks them as prominent constituents of prokaryotic genomes. Many plasmids are found in their host cell in multiple copies. This leads to an increased mutational supply of plasmid-encoded genes and genetically heterogeneous plasmid genomes. Nonetheless, the segregation of plasmid copies into daughter cells during cell division is considered to occur in the absence of selection on the plasmid alleles. We investigate the implications of random genetic drift of multicopy plasmids during cell division-termed here "segregational drift"-to plasmid evolution. Performing experimental evolution of low- and high-copy non-mobile plasmids in Escherichia coli, we find that the evolutionary rate of multicopy plasmids does not reflect the increased mutational supply expected according to their copy number. In addition, simulated evolution of multicopy plasmid alleles demonstrates that segregational drift leads to increased loss frequency and extended fixation time of plasmid mutations in comparison to haploid chromosomes. Furthermore, an examination of the experimentally evolved hosts reveals a significant impact of the plasmid type on the host chromosome evolution. Our study demonstrates that segregational drift of multicopy plasmids interferes with the retention and fixation of novel plasmid variants. Depending on the selection pressure on newly emerging variants, plasmid genomes may evolve slower than haploid chromosomes, regardless of their higher mutational supply. We suggest that plasmid copy number is an important determinant of plasmid evolvability due to the manifestation of segregational drift.
Topics: Biological Evolution; Chromosomes, Bacterial; Escherichia coli; Gene Frequency; Genetic Drift; Models, Genetic; Plasmids
PubMed: 30517696
DOI: 10.1093/molbev/msy225 -
Mathematical Biosciences and... Mar 2022Bacteria, in contrast to eukaryotic cells, contain two types of genes: chromosomal genes that are fixed to the cell, and plasmids, smaller loops of DNA capable of being...
Bacteria, in contrast to eukaryotic cells, contain two types of genes: chromosomal genes that are fixed to the cell, and plasmids, smaller loops of DNA capable of being passed from one cell to another. The sharing of plasmid genes between individual bacteria and between bacterial lineages has contributed vastly to bacterial evolution, allowing specialized traits to 'jump ship' between one lineage or species and the next. The benefits of this generosity from the point of view of both recipient cell and plasmid are generally understood: plasmids receive new hosts and ride out selective sweeps across the population, recipient cells gain new traits (such as antibiotic resistance). Explaining this behavior from the point of view of donor cells is substantially more difficult. Donor cells pay a fitness cost in order to share plasmids, and run the risk of sharing advantageous genes with their competition and rendering their own lineage redundant, while seemingly receiving no benefit in return. Using both compartment based models and agent based simulations we demonstrate that 'secretive' genes which restrict horizontal gene transfer are favored over a wide range of models and parameter values, even when sharing carries no direct cost. 'Generous' chromosomal genes which are more permissive of plasmid transfer are found to have neutral fitness at best, and are generally disfavored by selection. Our findings lead to a peculiar paradox: given the obvious benefits of keeping secrets, why do bacteria share information so freely?
Topics: Bacteria; Drug Resistance, Microbial; Gene Transfer, Horizontal; Phenotype; Plasmids
PubMed: 35603365
DOI: 10.3934/mbe.2022257 -
Microbiology Spectrum Aug 2022The horizontal transfer of genomic islands is essential for the adaptation and evolution of Enterococcus faecalis. In this study, three porcine E. faecalis strains, each...
The horizontal transfer of genomic islands is essential for the adaptation and evolution of Enterococcus faecalis. In this study, three porcine E. faecalis strains, each harboring a large (E)-carrying genomic island, were identified. When using the E. faecalis OG1RF as the recipient, the horizontal transfer of the (E)-carrying genomic island occurred only from E. faecalis E512, which also harbored a pheromone-responsive conjugative plasmid, but not from the other two E. faecalis strains, E533 and E509, which lacked such a plasmid. Subsequently, through plasmid curing of E. faecalis E512 and plasmid introduction into E. faecalis E533, the pheromone-responsive conjugative plasmid was identified to be indispensable for the horizontal transfer of the (E)-carrying genomic island and a subsequent homologous recombination between the chromosomal DNA of the donor and the recipient. In addition, the presence of a chromosomally-located conjugative transposon, Tn, in E. faecalis E509 could not mediate the horizontal transfer of the (E)-carrying genomic island, although Tn itself could transfer by conjugation. Thus, these data highlight the role of the pheromone-responsive conjugative plasmid in the transfer of the (E)-carrying genomic island in E. faecalis, thereby establishing the dual role of pheromone-responsive conjugative plasmids in contributing to the dissemination of both plasmid-borne resistance genes and chromosomally-located genomic islands. In this study, it was shown that a pheromone-responsive conjugative plasmid played an indispensable role in the horizontal transfer of a (E)-carrying genomic island. This finding indicates a dual role of the pheromone-responsive conjugative plasmid in disseminating both plasmid-borne resistance genes and chromosomally-located genomic islands. The role of the pheromone-responsive conjugative plasmid in disseminating chromosomal genomic islands is suggested to be essential in the genomic evolution of E. faecalis, which has become one of the leading nosocomial pathogens worldwide.
Topics: Animals; Conjugation, Genetic; Enterococcus faecalis; Genomic Islands; Pheromones; Plasmids; Swine
PubMed: 35863017
DOI: 10.1128/spectrum.00154-22 -
Biochemistry and Molecular Biology... Nov 2019This laboratory experiment describes the production and purification of plasmid DNA for undergraduate biochemistry and biotechnology courses. This experiment performed...
This laboratory experiment describes the production and purification of plasmid DNA for undergraduate biochemistry and biotechnology courses. This experiment performed in a one-week period includes the protocols for plasmid pVAX1-LacZ production in Escherichia coli DH5α cells and subsequent purification of supercoiled pVAX1-LacZ. Firstly, the students use a growth medium that favors the replication of the plasmid resulting in a higher plasmid production during exponential growth. Afterwards, alkaline lysis is done to disrupt the bacterial cells and recover pVAX1-LacZ plasmid. Lastly, they perform the purification of pVAX1-LacZ supercoiled isoform by L-histidine chromatography, followed by agarose gel electrophoresis to characterize the separation of supercoiled isoform from contaminants. The proposed experiment provides an opportunity for students to acquire these skills that are routinely used in biochemistry and biotechnology laboratories. © 2019 International Union of Biochemistry and Molecular Biology, 47(6):638-643, 2019.
Topics: Biochemistry; Biotechnology; Curriculum; DNA, Bacterial; Escherichia coli; Humans; Laboratories; Plasmids; Students; Universities
PubMed: 31390150
DOI: 10.1002/bmb.21290 -
MBio Jun 2023Plasmids facilitate the vertical and horizontal spread of antimicrobial resistance genes between bacteria. The host range and adaptation of plasmids to new hosts...
Plasmids facilitate the vertical and horizontal spread of antimicrobial resistance genes between bacteria. The host range and adaptation of plasmids to new hosts determine their impact on the spread of resistance. In this work, we explore the mechanisms driving plasmid adaptation to novel hosts in experimental evolution. Using the small multicopy plasmid pB1000, usually found in , we studied its adaptation to a host from a different bacterial family, Escherichia coli. We observed two different mechanisms of adaptation. One mechanism is single nucleotide polymorphisms (SNPs) in the origin of replication () of the plasmid, which increase the copy number in E. coli cells, elevating the stability, and resistance profile. The second mechanism consists of two insertion sequences (ISs), IS and IS, which decrease the fitness cost of the plasmid by disrupting an uncharacterized gene on pB1000 that is harmful to E. coli. Both mechanisms increase the stability of pB1000 independently, but only their combination allows long-term maintenance. Crucially, we show that the mechanisms have a different impact on the host range of the plasmid. SNPs in prevent the replication in the original host, resulting in a shift of the host range. In contrast, the introduction of ISs either shifts or expands the host range, depending on the IS. While IS leads to expansion, IS cannot be reintroduced into the original host. This study gives new insights into the relevance of ISs in plasmid-host adaptation to understand the success in spreading resistance. ColE1-like plasmids are small, mobilizable plasmids that can be found across at least four orders of and are strongly associated with antimicrobial resistance genes. Plasmid pB1000 carries the gene , conferring high-level resistance to penicillins and cefaclor. pB1000 has been described in various species of the family , for example, in Haemophilus influenzae, which can cause diseases such as otitis media, meningitis, and pneumonia. To understand the resistance spread through horizontal transfer, it is essential to study the mechanisms of plasmid adaptation to novel hosts. In this work we identify that a gene from pB1000, which encodes a peptide that is toxic for E. coli, and the low plasmid copy number (PCN) of pB1000 in E. coli cells are essential targets in the described plasmid-host adaptation and therefore limit the spread of pB1000-encoded . Furthermore, we show how the interplay of two adaptation mechanisms leads to successful plasmid maintenance in a different bacterial family.
Topics: DNA Transposable Elements; Escherichia coli; Plasmids; Bacteria; Cefaclor; Anti-Bacterial Agents
PubMed: 37097157
DOI: 10.1128/mbio.03158-22 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jan 2023Antimicrobial resistance has become a major public health issue of global concern. Conjugation is an important way for fast spreading drug-resistant plasmids, during... (Review)
Review
Antimicrobial resistance has become a major public health issue of global concern. Conjugation is an important way for fast spreading drug-resistant plasmids, during which the type Ⅳ pili plays an important role. Type Ⅳ pili can adhere on the surfaces of host cell and other medium, facilitating formation of bacterial biofilms, bacterial aggregations and microcolonies, and is also a critical factor in liquid conjugation. PilV is an adhesin-type protein found on the tip of type Ⅳ pili encoded by plasmid R64, and can recognize the lipopolysaccharid (LPS) molecules that locate on bacterial membrane. The shufflon is a clustered inversion region that diversifies the PilV protein, which consequently affects the recipient recognition and conjugation frequency in liquid mating. The shufflon was firstly discovered on an IncI1 plasmid R64 and has been identified subsequently in plasmids IncI2, IncK and IncZ, as well as the pathogenicity island of . The shufflon consists of four segments including A, B, C, and D, and a specific recombination site named sfx. The shufflon is regulated by its downstream-located recombinase-encoding gene , and different rearrangements of the shufflon region in different plasmids were observed. Mobile colistin resistance gene , which has attracted substantial attentions recently, is mainly located in IncI2 plasmid. The shufflon may be one of the contributors to fast spread of . Herein, we reviewed the discovery, structure, function and prevalence of plasmid mediated shufflon, aiming to provide a theoretical basis on transmission mechanism and control strategy of drug-resistant plasmids.
Topics: Plasmids; Proteins; Bacteria; Recombinases; Genes, Bacterial; Anti-Bacterial Agents
PubMed: 36738199
DOI: 10.13345/j.cjb.220343 -
MSphere Feb 2022Horizontal transfer of bacterial plasmids generates genetic variability and contributes to the dissemination of the genes that enable bacterial cells to develop...
Horizontal transfer of bacterial plasmids generates genetic variability and contributes to the dissemination of the genes that enable bacterial cells to develop antimicrobial resistance (AMR). Several aspects of the conjugative process have long been known, namely, those related to the proteins that participate in the establishment of cell-to-cell contact and to the enzymatic processes associated with the processing of plasmid DNA and its transfer to the recipient cell. In this work, we describe the roles of newly identified proteins that influence the conjugation of several plasmids. Genes encoding high-molecular-weight bacterial proteins that contain one or several immunoglobulin-like domains (Big) are located in the transfer regions of several plasmids that usually harbor AMR determinants. These Big proteins are exported to the external medium and target two extracellular organelles: the flagella and conjugative pili. The plasmid gene-encoded Big proteins facilitate conjugation by reducing cell motility and facilitating cell-to-cell contact by binding both to the flagella and to the conjugative pilus. They use the same export machinery as that used by the conjugative pilus components. In the examples characterized in this paper, these proteins influence conjugation at environmental temperatures (i.e., 25°C). This suggests that they may play relevant roles in the dissemination of plasmids in natural environments. Taking into account that they interact with outer surface organelles, they could be targeted to control the dissemination of different bacterial plasmids carrying AMR determinants. Transmission of a plasmid from one bacterial cell to another, in several instances, underlies the dissemination of antimicrobial resistance (AMR) genes. The process requires well-characterized enzymatic machinery that facilitates cell-to-cell contact and the transfer of the plasmid. Our paper identifies novel plasmid gene-encoded high-molecular-weight proteins that contain an immunoglobulin-like domain and are required for plasmid transmission. They are encoded by genes on different groups of plasmids. These proteins are exported outside the cell. They bind to extracellular cell appendages such as the flagella and conjugative pili. Expression of these proteins reduces cell motility and increases the ability of the bacterial cells to transfer the plasmid. These proteins could be targeted with specific antibodies to combat infections caused by AMR microorganisms that harbor these plasmids.
Topics: Anti-Infective Agents; Bacteria; Conjugation, Genetic; Gene Transfer, Horizontal; Immunoglobulin Domains; Plasmids
PubMed: 34986320
DOI: 10.1128/msphere.00978-21 -
Current Opinion in Microbiology Aug 2022Plasmids are a major driver of horizontal gene transfer in prokaryotes, allowing the sharing of ecologically important accessory traits between distantly related... (Review)
Review
Plasmids are a major driver of horizontal gene transfer in prokaryotes, allowing the sharing of ecologically important accessory traits between distantly related bacterial taxa. Within microbial communities, interspecies transfer of conjugative plasmids can rapidly drive the generation genomic innovation and diversification. Recent studies are starting to shed light on how the microbial community context, that is, the bacterial diversity together with interspecies interactions that occur within a community, can alter the dynamics of conjugative plasmid transfer and persistence. Here, I summarise the latest research exploring how community ecology can both facilitate and impose barriers to the spread of conjugative plasmids within complex microbial communities. Ultimately, the fate of plasmids within communities is unlikely to be determined by any one individual host, rather it will depend on the interacting factors imposed by the community in which it is embedded.
Topics: Bacteria; Conjugation, Genetic; Gene Transfer, Horizontal; Microbiota; Plasmids
PubMed: 35504055
DOI: 10.1016/j.mib.2022.102152