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F-plasmid
F-plasmid
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The F-plasmid (first named F by one of its discoverers Esther Lederberg；also called the sex factor in E. coli，the F sex factor, the fertility factor, or simply the F factor)[1][2][3] allows genes to be transferred from one bacterium carrying the factor to another bacterium lacking the factor by conjugation. The F factor was the first plasmid to be discovered. Unlike other plasmids, F factor is constitutive for transfer proteins due to a mutation in the gene finO.[4] The F plasmid belongs to F-like plasmids, a class of conjugative plasmids that control sexual functions of bacteria with a fertility inhibition (Fin) system.[5]

Discovery

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Esther M. Lederberg and Luigi L. Cavalli-Sforza discovered "F,"[6] subsequently publishing with Joshua Lederberg.[7] Once her results were announced, two other labs joined the studies. "This was not a simultaneous independent discovery of F (I named this as Fertility Factor until it was understood.) We wrote to Hayes, Jacob, & Wollman who then proceeded with their studies."[8] The discovery of "F" has sometimes been confused with William Hayes' discovery of "sex factor", though he never claimed priority. Indeed, "he [Hayes] thought F was really lambda, and when we convinced him [that it was not], he then began his work."[9]

Structure

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The most common functional segments constituting F factors are:[10]

  • OriT (Origin of Transfer): The sequence which marks the starting point of conjugative transfer.
  • OriV (Origin of Vegetative Replication): The sequence starting with which the plasmid-DNA will be replicated in the recipient cell.
  • tra-region (transfer genes): Genes coding the F-Pilus and DNA transfer process.
  • IS (Insertion Elements) composed of one copy of IS2, two copies of IS3, and one copy of IS1000: so-called "selfish genes" (sequence fragments which can integrate copies of themselves at different locations).[11]

Some F plasmid genes and their Function:

  • traA: F-pilin, Major subunit of the F-pilus.
  • traN: recognizes cell-surface receptors[5]

Relation to the genome

[edit]

The episome that harbors the F factor can exist as an independent plasmid or integrate into the bacterial cell's genome. There are several names for the possible states:

  • Hfr bacteria possess the entire F episome integrated into the bacterial genome.
  • F+ bacteria possess F factor as a plasmid independent of the bacterial genome. The F plasmid contains only F factor DNA and no DNA from the bacterial genome.
  • F' (F-prime) bacteria are formed by incorrect excision from the chromosome, resulting in F plasmid carrying bacterial sequences that are next to where the F episome has been inserted.
  • F− bacteria do not contain F factor and act as the recipients.

Function

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When an F+ cell conjugates/mates with an F− cell, the result is two F+ cells, both capable of transmitting the plasmid to other F− cells by conjugation. A pilus on the F+ cell interacts with the recipient cell allowing formation of a mating junction, the DNA is nicked on one strand, unwound and transferred to the recipient.[3][10]

The F-plasmid belongs to a class of conjugative plasmids that control sexual functions of bacteria with a fertility inhibition (Fin) system. In this system, a trans-acting factor, FinO, and antisense RNAs, FinP, combine to repress the expression of the activator gene TraJ. TraJ is a transcription factor that upregulates the tra operon. The tra operon includes genes required for conjugation and plasmid transfer. This means that an F+ bacteria can always act as a donor cell. The finO gene of the original F plasmid (in E. coli K12) is interrupted by an IS3 insertion, resulting in constitutive tra operon expression.[12][13] F+ cells also have the surface exclusion proteins TraS and TraT on the bacterial surface. These proteins prevent secondary mating events involving plasmids belonging to the same incompatibility (Inc) group. Thus, each F+ bacterium can host only a single plasmid type of any given incompatibility group.

In the case of Hfr transfer, the resulting transconjugates are rarely Hfr. The result of Hfr/F−conjugation is a F− strain with a new genotype. When F-prime plasmids are transferred to a recipient bacterial cell, they carry pieces of the donor's DNA that can become important in recombination. Bioengineers have created F plasmids that can contain inserted foreign DNA; this is called a bacterial artificial chromosome.

The first DNA helicase ever described is encoded on the F-plasmid and is responsible for initiating plasmid transfer. It was originally called E. coli DNA Helicase I, but is now known as F-plasmid TraI. In addition to being a helicase, the 1756 amino acid (one of the largest in E. coli) F-plasmid TraI protein is also responsible for both specific and non-specific single-stranded DNA binding as well as catalyzing the nicking of single-stranded DNA at the origin of transfer.

See also

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References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

F-plasmid

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from Grokipedia
The F-plasmid, also known as the fertility factor or F factor, is a conjugative plasmid primarily found in that enables between through the process of conjugation. This circular, double-stranded DNA molecule is approximately 100 kb in length and carries essential genes for its autonomous replication, stable partitioning during cell division, and mobilization for transfer to recipient cells via a type IV secretion system (T4SS). First evidenced in 1946 through experiments demonstrating in mixed cultures of E. coli auxotrophic mutants by and Edward L. Tatum, the F-plasmid was later identified in the early 1950s as the transmissible "sex factor" responsible for the donor phenotype in conjugation. The plasmid's structure includes a core maintenance region for replication (centered around the repE ori and dnaA-independent replication genes) and a partition system ensuring equal distribution to daughter cells, alongside the tra operon—a large cluster of about 40 genes spanning roughly 33 kb that orchestrates conjugation. Key components of the tra region include oriT (the origin of transfer, a ~300-bp region containing the nick site), traJ (a transcriptional activator), traA (encoding the pilin subunit for F-pilus assembly), traI (the relaxase enzyme that nicks DNA at oriT), and accessory genes like traM and traY forming the relaxosome complex for DNA processing. During conjugation, the F-plasmid directs the formation of a conjugative pilus—a thin, flexible protein filament up to 20 µm long—that bridges donor and recipient cells, allowing single-stranded DNA transfer at rates up to 400-600 nucleotides per second, followed by complementary strand synthesis in the recipient. Notably, the F-plasmid can integrate into the bacterial chromosome via IS elements, forming high-frequency recombination (Hfr) strains that transfer chromosomal DNA, or exist extrachromosomally in F+ cells, influencing bacterial evolution by disseminating traits like antibiotic resistance and virulence factors.

History

Discovery

In 1946, Joshua Lederberg and Edward L. Tatum conducted pioneering experiments demonstrating in . Using auxotrophic mutants unable to synthesize specific nutrients, they mixed two strains—one requiring and , the other requiring and —and observed rare prototrophic recombinants capable of growth on minimal media. This unexpected result indicated that bacteria could exchange genetic material in a manner analogous to in eukaryotes, prompting a search for an underlying "sex factor" responsible for the phenomenon. Building on this, Bernard Davis in 1950 devised U-tube experiments to investigate the mechanism of genetic transfer. The U-tube apparatus featured a sintered glass filter at its bend, allowing the free passage of media and diffusible substances but preventing direct cell contact between the two arms. When auxotrophic strains were placed in separate arms, no recombinants appeared, whereas mixing the strains without the filter yielded them. These findings established that physical contact between donor and recipient cells was essential for transfer, and Davis identified "male" (F⁺) strains that acted as donors and "female" (F⁻) strains as recipients in this contact-dependent process. Further confirmation came in 1952 through the work of , who observed conversions of F⁻ cells to F⁺ in mixed cultures of the two strains. This indicated the involvement of a transmissible genetic element. Collaborating with Luigi Cavalli-Sforza, she named this element the "Fertility Factor" (F), establishing it as a heritable entity that conferred donor ability to F⁺ cells and enabled unidirectional transfer during bacterial mating. Their experiments, including selective plating techniques, provided initial evidence that the F factor was stably maintained and propagated independently in the bacterial population.

Historical Significance

The discovery of the F-plasmid, also known as the F factor or fertility factor, marked a pivotal moment in bacterial genetics as the first recognized extrachromosomal genetic element capable of independent replication and transmission. In the early 1950s, researchers Joshua Lederberg and William Hayes identified the F factor in Escherichia coli as the agent responsible for the "male" fertility phenotype in bacterial conjugation experiments, challenging the prevailing view that genetic inheritance in bacteria occurred solely through chromosomal mechanisms. This revelation shifted paradigms by introducing the concept of plasmids—self-replicating DNA molecules separate from the chromosome—coined by Lederberg in 1952, thereby expanding the understanding of genetic stability and variability in prokaryotes. The F-plasmid profoundly influenced the study of horizontal gene transfer, establishing bacterial conjugation as a foundational model that paralleled sexual reproduction in eukaryotes. Through experiments in the 1950s, Lederberg, Hayes, François Jacob, and Élie Wollman demonstrated that the F-plasmid mediated direct cell-to-cell DNA transfer, enabling the exchange of genetic material between bacteria without viral intermediaries. This process not only elucidated mechanisms of genetic recombination but also highlighted conjugation's role in rapid evolutionary adaptation, laying groundwork for broader investigations into microbial gene flow. In the and , the F-plasmid's integration into the E. coli to form high-frequency recombination (Hfr) strains revolutionized bacterial mapping. and Wollman pioneered the interrupted mating technique, using Hfr donors to transfer chromosomal segments sequentially into recipient cells, allowing precise determination of order and distances based on transfer timing. Their work, detailed in seminal studies, produced the first comprehensive genetic map of the E. coli , confirming its circular nature and facilitating the localization of hundreds of s, which became a cornerstone for research. The F-plasmid also catalyzed the establishment of plasmid classification systems, distinguishing conjugative plasmids like F—which encode their own transfer machinery—from non-conjugative ones, a framework developed in the and . This distinction proved instrumental in early studies of resistance, as Japanese researchers in the late identified resistance (R) factors as conjugative plasmids akin to F, revealing how such elements rapidly disseminated multidrug resistance genes among bacterial populations and foreshadowing challenges.

Structure and Genetic Organization

Physical Structure

The F-plasmid is an extrachromosomal, circular double-stranded DNA molecule with a size of approximately 100 kb (99,159 bp). This compact architecture allows it to function autonomously within the bacterial cell while enabling interactions with the host genome. The complete nucleotide sequence reveals a highly organized structure, with the circular form ensuring stable maintenance and efficient replication independent of the chromosomal DNA. In its native state within cells, the F-plasmid predominantly exists in a supercoiled conformation, a topological state generated and maintained by host enzymes such as . This supercoiling compacts the DNA, facilitates regulatory processes, and contributes to the plasmid's overall stability. However, during specific cellular events like replication initiation or conjugative transfer, the plasmid can transiently adopt relaxed or nicked forms to accommodate strand unwinding and processing by relaxase enzymes. Measurements of supercoiling density indicate that the F-plasmid retains a significant portion of its superhelical turns even under conditions inhibiting gyrase activity, underscoring the dynamic yet constrained of this molecule. The F-plasmid harbors multiple insertion sequence (IS) elements, including one copy of (~1.3 kb), two copies of (~1.3 kb each), and one IS1000 (also known as Tn1000 or γδ, ~5.7 kb), which collectively account for roughly 10% of the plasmid's length. These are dispersed across the and promote structural variability through recombination, though their precise positioning supports the plasmid's core functions without disrupting essential regions. As a low-copy-number , the F-plasmid is typically maintained at 1-2 copies per cell in F⁺ strains, a controlled abundance that minimizes metabolic burden on the host while ensuring reliable inheritance during .

Key Genetic Elements

The F-plasmid, also known as the fertility factor, harbors several key genetic elements that orchestrate its replication, stable maintenance, and conjugative transfer capabilities. Central to its conjugative functions is the tra region, a large transfer spanning approximately 33 kb and encoding more than 40 genes. This includes genes such as traA, which encodes the pilin subunit for the sex assembly; traI, responsible for the relaxase/ activity that nicks DNA at the origin of transfer; and traN, which facilitates recipient cell recognition during pair stabilization. Other notable genes within the tra region, like traD and traG, contribute to the type IV secretion system (T4SS) machinery for DNA translocation, while traS and traT mediate surface and entry exclusion to prevent redundant transfers. These elements collectively enable the plasmid's donor functions without delving into the mechanistic steps of transfer. For autonomous replication, the F-plasmid relies on the origin of vegetative replication (oriV), a compact sequence of about 400 bp that serves as the site for initiation of plasmid DNA synthesis. Associated with oriV are control genes such as repE, which encodes the RepE initiator protein that binds to iterons within oriV to recruit host replication machinery, and ssf (also referred to as the plasmid-encoded single-stranded DNA-binding protein gene), which provides SSB-like activity to stabilize single-stranded DNA intermediates during replication. This replication module ensures the plasmid maintains a low copy number (typically 1-2 per cell) in Escherichia coli hosts. The origin of transfer (oriT) is another critical element, consisting of a ~300 sequence that includes the nic site where the TraI relaxase introduces a site-specific nick to initiate single-stranded DNA transfer during conjugation. OriT also contains binding sites for relaxosome proteins, facilitating the assembly of the transfer apparatus. Stable inheritance of the F-plasmid during host is governed by partitioning genes, primarily the sop locus (also known as par), which includes sopA and sopB encoding partitioning proteins and the cis-acting sopC centromere-like region. SopA acts as an that energizes plasmid segregation, while SopB serves as a DNA-binding adaptor, ensuring equitable distribution to daughter cells and minimizing loss rates to below 0.01% per generation. Regulation of the tra is modulated by the finP and finO elements, which implement inhibition to fine-tune conjugation frequency in many IncF plasmids. finP encodes a small antisense (~100 ) that base-pairs with traJ mRNA to repress translation of the TraJ transcriptional activator, thereby dampening tra expression. The finO gene produces an that stabilizes finP, enhancing its inhibitory effect and preventing untimely activation of the transfer machinery. However, in the standard F , finO is interrupted by an IS3 insertion, rendering it non-functional and resulting in constitutive tra expression. This leads to high conjugation frequency in F+ strains, influencing dissemination without the balancing inhibition seen in other related plasmids.

Interaction with Bacterial Genome

Plasmid Maintenance

The F-plasmid maintains its extrachromosomal state in through tightly controlled replication and an active partitioning system that ensures stable inheritance during , typically at 1–2 copies per cell. Replication initiates at the vegetative (OriV), where the plasmid-encoded RepE protein binds to specific iterons and recruits host factors, including and DnaB helicase, to promote bidirectional theta-type replication. Copy number is autoregulated by RepE itself: monomeric RepE functions as the replication initiator, while dimeric RepE binds to inverted repeats in the repE promoter-operator region, repressing further transcription of the repE gene and preventing excessive replication. This negative feedback mechanism maintains low copy number without reliance on antisense RNA, distinguishing it from other plasmid families like ColE1. Stable partitioning is mediated by the sopABC locus, where SopB binds as a dimer to the centromere-like sopC DNA region, forming a partition complex that interacts with the SopA to actively segregate plasmid copies to daughter cells. SopA forms dynamic filaments that facilitate plasmid movement toward the poles or midcell, ensuring near-random or better-than-random distribution independent of chromosomal partitioning. This system minimizes segregation errors, contributing to the plasmid's high fidelity in dividing cells. The F-plasmid functions as an autonomous replicon compatible with the E. coli , exhibiting no extensive to the host chromosome except for a limited number of insertion sequence (IS) elements such as and , which do not interfere with episomal maintenance under standard conditions. In F+ cells, the plasmid exhibits high stability, leveraging host pathways to sustain a low comparable to the chromosomal level, though rare partitioning failures or physiological stresses can occasionally result in plasmid loss and reversion to the F- at rates below 10^{-3} per generation. Additional stabilization arises from post-segregational killing systems like ccdAB, where the CcdB toxin eliminates plasmid-free segregants unless neutralized by CcdA .

Integration Mechanisms

The integration of the F-plasmid into the chromosome occurs primarily through mediated by insertion sequence (IS) elements shared between the plasmid and the bacterial genome, such as and . These IS elements, which are short DNA segments of approximately 1.3 kb () and 1.25 kb (), provide regions of that facilitate RecA-dependent recombination, allowing the circular F-plasmid to insert at multiple chromosomal loci. This process was elucidated through electron microscopic analysis of heteroduplex DNA molecules from Hfr strains, revealing that the integrated F sequences are flanked by IS elements at both junctions with the chromosome. The resulting high-frequency recombination (Hfr) strains exhibit the F-plasmid integrated in a specific orientation, with the origin of transfer (oriT) positioned proximal to the chromosomal leading region, enabling unidirectional transfer of chromosomal DNA during conjugation starting from oriT and proceeding through adjacent bacterial genes. Integration sites are determined by the distribution of homologous IS elements in the , with common hotspots near genes like lac or pro, and the frequency of integration varies between IS types; for instance, IS2-mediated events occur at higher rates than in certain intergenic regions. This mechanism, first inferred from genetic mapping in the and confirmed molecularly in the , transforms F+ cells into Hfr donors capable of transferring up to nearly the entire , though complete transfer is rare due to conjugation bridge breakage. Excision of the integrated F-plasmid can generate F' (F-prime) plasmids through imprecise recombination between IS elements, where the excision event incorporates adjacent chromosomal DNA into the autonomous plasmid, creating partial diploids useful for genetic complementation studies. For example, recombination between an on the F-plasmid and a chromosomal near the yields F'lac, carrying bacterial lac genes. Precise excision, restoring the wild-type F-plasmid without bacterial DNA, occurs via recombination between the identical IS elements at the integration junctions, reverting Hfr cells to the F+ state at low frequency (approximately 10^{-5} to 10^{-4} per generation). These reversible integration and excision events highlight the dynamic role of IS-mediated recombination in F-plasmid mobility.

Functions in Conjugation

Transfer Process

The transfer process of the F-plasmid during bacterial conjugation involves a series of coordinated steps that enable the unidirectional transfer of a single-stranded DNA copy from a donor cell (F+) to a recipient cell (F-). This mechanism relies on the tra operon genes, which encode proteins essential for pilus assembly, mating pair formation, DNA processing, and translocation through a type IV secretion system (T4SS). The process initiates upon physical contact between donor and recipient cells, ensuring efficient horizontal gene transfer in Gram-negative bacteria like Escherichia coli. Pilus formation begins with the traA gene encoding a 121-amino-acid pro-pilin precursor, which is processed into a mature 70-amino-acid F-pilin subunit by the chaperone TraQ and leader peptidase TraX. These pilin monomers self-assemble at the inner membrane into a thin, flexible F-pilus (approximately 8 nm in diameter and up to 20 μm in length), extending from the donor cell surface to establish initial contact with the recipient. The pilus assembly is Sec-independent and powered by the proton motive force, with TraL anchoring the pilus base to the inner membrane. Once contact is made, the pilus retracts or forms a stable mating junction, transitioning to mating pair stabilization mediated by TraN, an outer membrane protein in the donor that interacts with the recipient's OmpA porin and lipopolysaccharide (LPS). This bridging enhances cell-cell adhesion and positions the T4SS for DNA transfer. At the origin of transfer (oriT) site on the F-plasmid, DNA processing occurs within a nucleoprotein complex called the relaxosome, formed by host integration host factor (IHF), , , and the bifunctional TraI protein. TraI acts as both a relaxase, nicking the DNA at oriT to generate a 5'-phosphotyrosine covalent intermediate and a free 3'-OH end, and a , unwinding the DNA for transfer. The relaxosome docks to the T4SS via TraD, a type IV protein (T4CP) that recruits the single-stranded DNA (ssDNA)-TraI complex to the transfer channel, while TraG couples the relaxosome to the apparatus for stabilization. The nicked leading strand (T-strand) is then translocated 5' to 3' through the T4SS channel into the recipient, powered by TraI activity and by VirB4-like motors (TraB, TraE, etc.). In the donor, rolling-circle replication (RCR) regenerates the complementary strand using the F-plasmid's RepE protein, ensuring the donor retains a complete copy. In the recipient cell, the transferred T-strand, still bound to TraI, is circularized by TraI's ligation activity, forming a closed ssDNA circle coated by host single-stranded DNA-binding protein (SSB). The F-plasmid's Frpo promoter then directs host RNA polymerase to synthesize short RNA primers, allowing host DNA polymerase III to elongate and synthesize the complementary strand, ultimately restoring a double-stranded F-plasmid that can replicate autonomously. Transfer efficiency is nearly 100% for the complete F-plasmid in F+ × F- matings under optimal liquid culture conditions, reflecting the process's high fidelity. In contrast, when the F-plasmid is integrated into the chromosome (Hfr strain), transfer initiates similarly but proceeds linearly through chromosomal DNA, resulting in only partial transfer (typically <1% for the full chromosome) due to mating pair disruption before completion.

Regulatory Mechanisms

The regulatory mechanisms of the F-plasmid primarily revolve around the FinO/FinP system, which controls the expression of conjugation functions through post-transcriptional repression of the key activator gene traJ. FinP is a small antisense (approximately 79 nucleotides) encoded on the F-plasmid that base-pairs with the (UTR) of traJ mRNA, forming a stable duplex that blocks ribosomal access and leads to degradation of the mRNA by RNase III, thereby inhibiting TraJ protein synthesis. FinO, a plasmid-encoded and chaperone, enhances this repression by binding to stem-loop structures in both FinP and traJ mRNA, stabilizing the antisense duplex and extending the half-life of FinP, which collectively prevents constitutive activation of conjugation genes. TraJ serves as the master positive regulator of the F-plasmid's transfer (tra) , a large cluster of genes (over 30) responsible for conjugation machinery. Upon sufficient TraJ accumulation, it binds as a dimer to an upstream in the tra promoter (P_tra), recruiting to initiate transcription and coordinating the expression of downstream genes essential for formation and DNA transfer. This hierarchical control ensures that conjugation is inducible rather than perpetually active, with TraJ levels directly determining the timing and extent of tra . The FinO/FinP system contributes to density-dependent regulation of conjugation, exhibiting quorum-sensing-like inhibition in high-density bacterial populations where transfer rates are reduced to prevent excessive dissemination. This modulation optimizes maintenance by limiting energy expenditure on unnecessary transfers when donor cells are abundant. Mutations disrupting the FinO/FinP system, such as the insertion of the transposon into the finO gene in the prototypical F-plasmid, abolish repression and result in constitutive TraJ expression, leading to significantly elevated conjugation frequencies (up to 100-fold higher than in repressed states). These finO- mutants highlight the system's role in fine-tuning transfer efficiency, as restored FinO function in compatible plasmids reinstates inhibition.

Applications and Broader Impact

Role in Bacterial Genetics

The F-plasmid plays a pivotal role in bacterial genetics by enabling the interrupted mating technique with high-frequency recombination (Hfr) strains, which facilitates time-of-entry mapping of the Escherichia coli chromosome. In this method, Hfr donor cells, where the F-plasmid is integrated into the bacterial chromosome, transfer chromosomal DNA linearly to F⁻ recipient cells during conjugation at a relatively constant rate of approximately 1 minute per 1% of the genome. By mechanically interrupting the mating process at timed intervals using a blender and then selecting for transferred markers, researchers can determine the order and relative positions of genes based on their entry times from a fixed origin of transfer. This approach established the circular nature of the E. coli chromosome and mapped key loci, such as those for galactose utilization (entering at about 17 minutes) and tryptophan biosynthesis (around 27 minutes), providing a foundational framework for bacterial genome organization. F' plasmids, autonomous derivatives of the F-plasmid carrying segments of chromosomal DNA, have been instrumental in complementation analysis to elucidate gene functions through the creation of partial diploids. When an F' plasmid harboring a wild-type is introduced into a recipient strain, the extra copy allows phenotypic restoration if the mutations are in different genes, confirming complementation groups and distinguishing cis- from elements. For instance, in studies of the , F'lac plasmids enabled the formation of merodiploids that demonstrated the dominance of certain regulatory mutations, revealing mechanisms of control. This technique, pioneered in the early 1960s, has been essential for dissecting complex pathways without relying on full chromosomal replacement. The F-plasmid's mediation of conjugation transformed bacterial by establishing "bacterial " as a powerful tool for gene transfer, , and selection studies. Conjugation allows targeted introduction of donor DNA into recipients, facilitating the generation of recombinant strains for and the isolation of rare mutants through selective media. This system enabled large-scale genetic screens, such as those identifying auxotrophic mutants or testing for suppressor effects, accelerating the understanding of metabolic and regulatory networks in . Insights from the F-plasmid significantly influenced the of lysogeny and , drawing parallels between conjugative plasmids and temperate phages like . The autonomous yet integrative behavior of the F-plasmid exemplified the episome model, where extrachromosomal elements can excise or insert, mirroring the state of and unifying viral and . This linkage, developed through comparative studies, highlighted shared mechanisms of replication control and genetic mobilization, shaping models for in prokaryotes.

Modern Molecular Biology Uses

Post-2020 advancements have integrated F-plasmid conjugation with -Cas systems to enable targeted horizontal gene editing, particularly for combating antibiotic-resistant pathogens. In the targeted-antibacterial-plasmid (TAP) approach, the F-plasmid's tra genes drive the transfer of a conjugative plasmid encoding a -Cas9 module, which specifically cleaves resistance genes in recipient cells, leading to their selective elimination. This system achieves high transfer rates (up to 10^{-1} transconjugants per donor) in and extends to other , allowing precise editing of without off-target effects on commensal . Such conjugative delivery has been demonstrated to resensitize multidrug-resistant strains to antibiotics like , highlighting its potential in therapeutics. Recent genomic surveillance as of 2023 has underscored the role of F-like plasmids in disseminating resistance, with F-type plasmids carrying approximately 42.5% of genes, including extended-spectrum beta-lactamases (ESBLs), in human-associated isolates. These plasmids evolve through recombination, integrating resistance cassettes and facilitating interspecies transfer in clinical settings like infections.

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