What is horizontal gene transfer in bacteria?

Bacteria can acquire new genetic information without producing offspring. Under suitable conditions, a bacterial cell can receive DNA originating from another organism through a process known as horizontal gene transfer.

This is different from vertical gene transfer, in which genetic information passes from a parent cell to its descendants during reproduction.

Horizontal gene transfer is important because bacteria can acquire genetic material that was not present in their immediate ancestors. The acquired DNA may carry genes involved in nutrient use, environmental adaptation, defence against bacteriophages or antibiotic resistance.

Three mechanisms are commonly taught in microbiology: transformation, transduction and conjugation.

Transformation involves the uptake of DNA from the surrounding environment. Transduction involves bacteriophages carrying bacterial genetic material between cells. Conjugation involves DNA transfer through direct contact between a donor and a recipient.

These mechanisms differ in how DNA moves, what molecular machinery is required and which barriers must be overcome before the acquired genetic material becomes established.

DNA entering a cell does not necessarily become part of its heritable genetic material. It must escape degradation and either integrate into a replicating DNA molecule or be maintained independently to persist across generations.

Figure: This conceptual figure was created by AI for Microbes World.

How is horizontal gene transfer different from mutation?

Mutation and horizontal gene transfer both contribute to bacterial genetic variation, but they operate differently.

A mutation changes an existing DNA sequence. It may arise through replication errors, DNA damage or other molecular processes. Mutations can alter protein function, gene expression or regulatory activity.

Horizontal gene transfer introduces genetic material from another biological source. Depending on the mechanism, this may involve a small DNA fragment, an entire plasmid or a larger mobile genetic element.

For example, a bacterium might become less susceptible to an antibiotic because a mutation changes the antibiotic's cellular target. Alternatively, it might acquire a gene encoding an enzyme capable of modifying or inactivating the antibiotic.

Both outcomes can contribute to resistance, but the genetic origins differ: one modifies a gene already present, whereas the other introduces genetic material from elsewhere.

Horizontal gene transfer also does not guarantee an advantage. Newly acquired DNA may have no measurable effect, interfere with cellular processes or impose a metabolic cost. Whether the DNA persists depends on its compatibility with the host, its maintenance mechanisms and the surrounding environment.

This distinction helps explain why the presence of a mobile genetic element does not automatically indicate that the host bacterium has become more competitive or pathogenic.

Transformation: Taking up DNA from the environment

Natural transformation occurs when a bacterium takes up extracellular DNA through specialized cellular machinery.

DNA may become available after bacterial cell lysis or through other processes that release genetic material into the environment. However, extracellular DNA does not automatically enter every nearby bacterial cell.

For natural transformation, a bacterium needs suitable DNA-uptake machinery and a physiological state that permits its operation, known as competence. The timing and regulation of competence vary between species.

In naturally competent bacteria, surface-associated proteins help capture DNA and transport it across the cell envelope. In many well-characterized systems, one DNA strand is degraded during uptake while the other enters the cytoplasm.

The incoming DNA may subsequently be incorporated into the chromosome through homologous recombination, provided that sufficient sequence similarity and appropriate recombination machinery are present.

In some systems, incoming DNA can also be established as a plasmid if it has the necessary replication functions and is compatible with the recipient.

How does incoming DNA become part of a bacterial chromosome?

DNA uptake and DNA integration are separate molecular events.

When an incoming DNA fragment shares substantial sequence similarity with a region of the recipient chromosome, homologous recombination can replace or modify the corresponding chromosomal sequence.

Proteins involved in DNA protection and recombination help guide this process.

A 2025 study by Dalia and colleagues investigated the interaction between two proteins, DprA and ComM, during natural transformation.

Using Helicobacter pylori and Vibrio cholerae as experimental models, the researchers combined structural predictions, protein-interaction assays and genetic experiments.

They found that interactions between DprA and ComM support the recruitment of ComM during the recombination process. Disrupting the interaction impaired natural transformation in the tested systems.

The experiments provide mechanistic evidence for coordination between proteins involved in the recombination of incoming DNA.

It does not mean that all bacterial species use identical transformation machinery. Natural competence, DNA recognition and recombination mechanisms differ among bacterial groups.

Transduction: When bacteriophages move bacterial DNA

Bacteriophages are viruses that infect bacteria. During their replication cycles, some phages can transfer bacterial genetic material from one cell to another.

The transfer of bacterial DNA by bacteriophage particles is known as transduction.

A phage normally delivers its own genetic material into a susceptible bacterial host. However, under certain circumstances, phage particles can carry DNA originating from a previous bacterial host.

If that DNA reaches another bacterium and becomes established, horizontal gene transfer has occurred.

Generalized transduction

In classical generalized transduction, fragments of bacterial DNA can be mistakenly packaged into phage-derived particles during phage production.

The resulting particles can deliver bacterial DNA to another susceptible cell.

Because packaging errors can involve different regions of the donor chromosome, generalized transduction can potentially transfer a range of bacterial genes, although packaging constraints and phage biology impose important limitations.

Successful transfer also depends on the recipient's ability to retain or recombine the delivered DNA.

Specialized transduction

Specialized transduction is associated with particular temperate phages that integrate into bacterial chromosomes.

When an integrated phage genome is excised, an abnormal excision event can occasionally include adjacent bacterial DNA.

That DNA may then be carried into another bacterial host during subsequent infection.

Unlike generalized transduction, the classical specialized mechanism is restricted by the location of the integrated phage and the DNA neighbouring its integration site.

Phage-mediated genetic transfer is therefore not one uniform process. Its mechanism and range depend on the phage, the bacterial host and the organization of the genetic material.

Does every phage infection transfer bacterial genes?

No. Phage infection alone is not evidence of horizontal gene transfer. A bacteriophage may simply replicate and produce progeny, enter a persistent relationship with its host or fail to establish infection.

Even when bacterial DNA is packaged into a phage particle, successful delivery and stable inheritance are not guaranteed.

This is particularly important when interpreting bacteriophage research. Detecting phage DNA or observing bacterial killing does not independently demonstrate that bacterial genes were transferred.

Conjugation: DNA transfer through bacterial contact

Conjugation occurs when genetic material moves between bacterial cells through specialized transfer machinery.

The process usually requires close contact between a donor and a recipient.

Conjugative plasmids are well-known participants in this mechanism. These DNA molecules contain functions that allow them to initiate transfer and, in suitable hosts, replicate independently of the bacterial chromosome.

In many Gram-negative bacterial systems, a conjugative pilus helps establish or stabilize interactions between cells. DNA is then transferred through a specialized secretion apparatus, commonly involving a type IV secretion system.

The DNA-processing enzyme relaxase recognizes a transfer origin, usually called oriT, and initiates the transfer process.

Transfer often involves a single DNA strand, which is subsequently converted into double-stranded DNA in the recipient.

The exact transfer machinery differs among bacterial lineages and mobile elements. It would therefore be misleading to suggest that every bacterial conjugation event uses an identical pilus or that DNA simply passes through a hollow pilus in every system.

Are all plasmids conjugative?

No. A conjugative plasmid contains the functions required to mediate its own transfer under appropriate conditions.

A mobilizable plasmid may carry a transfer origin and some DNA-processing functions but lack a complete transfer apparatus. It can sometimes use machinery supplied by another compatible mobile element in the same cell.

Other plasmids lack the necessary transfer functions and cannot be assumed to move by conjugation.

The distinction matters when analysing bacterial genomes. Finding a plasmid sequence does not establish that the plasmid is self-transmissible.

Likewise, finding genes associated with conjugation does not prove that transfer occurred under the conditions being studied.

Horizontal gene transfer is not limited to plasmids

Plasmids are important, but bacterial chromosomes can also contain mobile genetic elements capable of moving between cells.

Integrative and conjugative elements, or ICEs, can reside within bacterial chromosomes. Under suitable conditions, they can excise, undergo conjugative transfer and integrate into a recipient genome.

Integrative and mobilizable elements, or IMEs, also integrate into chromosomes but generally depend on transfer machinery supplied by another element.

A study published in Scientific Reports in May 2025 illustrates why these elements deserve attention.

Guédon and colleagues examined four complete genomes belonging to the human gut bacterial genus Faecalibacterium.

Although the four genomes lacked plasmids, the researchers identified 17 integrative and conjugative elements and 83 integrative and mobilizable elements, along with other related mobile sequences.

The identified elements collectively represented approximately 14–23% of the analysed genomes.

The researchers identified nearly identical mobile elements in Faecalibacterium and Roseburia strains isolated from the same faecal sample, providing genomic evidence consistent with horizontal transfer.

However, these were primarily comparative genomic findings. Sequence similarity can support an inference of historical transfer, but it does not directly measure the frequency of conjugation occurring in the human intestine at the time of sampling.

This illustrates why examining plasmids alone can miss chromosomally integrated mobile elements. The term mobilome refers to the collection of mobile genetic elements associated with a genome or community.

How efficiently can bacteria exchange genes in the gut?

The intestinal microbiome contains many bacterial populations living in close proximity, making it an important environment for investigating genetic exchange.

However, close proximity does not guarantee efficient transfer.

In a 2020 study, Neil and colleagues evaluated 13 conjugative plasmids representing 10 incompatibility groups in a mouse intestinal model.

Most of the tested plasmids transferred poorly or were not detectably transferred under the experimental conditions.

One plasmid, TP114, performed particularly well. The researchers identified a type IV pilus-associated function important for its transfer in the mouse gut.

Their results also showed that transfer performance depended on the experimental environment; the mouse-gut result should not be extrapolated from standard culture conditions.

The differences highlight how strongly conjugation depends on the plasmid and the surrounding conditions.

This was an experimental mouse study, not a measurement of universal plasmid-transfer rates in human gut microbiomes.

Transfer efficiency therefore needs to be tested in the biological setting relevant to the research question.

Can bacteriophages indirectly influence conjugation?

The three horizontal gene transfer mechanisms are usually presented separately, but their ecological interactions can be more complicated.

A 2024 study by Ruan and colleagues investigated plasmid transfer between two Escherichia coli strains growing together on laboratory surfaces.

The researchers used a conjugative plasmid, R388, and compared bacterial communities exposed or not exposed to a lytic bacteriophage.

Unexpectedly, phage exposure increased the spread of the plasmid under their experimental conditions.

The explanation was not that the phage carried the plasmid between bacteria.

Instead, phage predation altered the spatial organization of the growing bacterial populations. This maintained more opportunities for donor and recipient cells to interact, increasing conjugation-mediated plasmid transfer.

The researchers specifically examined whether transformation or transduction could account for the observed result and found no evidence that either explained the increase in their experimental system.

This distinction is important: a bacteriophage can influence horizontal gene transfer without directly serving as the vehicle carrying the transferred DNA.

The study used a defined laboratory system involving E. coli, plasmid R388 and bacteriophage T6. It does not establish that phage exposure generally increases antibiotic resistance in natural environments or during clinical phage therapy.

Why do biofilms matter for bacterial gene exchange?

Biofilms are microbial communities in which cells may be embedded within an extracellular matrix containing polysaccharides, proteins and extracellular DNA.

These environments can create opportunities for genetic exchange.

Extracellular DNA can provide material for transformation in competent organisms. Close contact between neighbouring cells can facilitate conjugation. Bacteriophages may also interact with bacterial populations within biofilms.

However, biofilm formation does not necessarily increase every type of horizontal gene transfer.

The extracellular matrix may influence DNA availability and phage movement, while the spatial arrangement of bacterial populations can either increase or reduce encounters between compatible donors and recipients.

The physiological state of the cells also matters. Nutrient limitation, oxygen gradients, growth rates and regulatory responses can influence the expression and operation of transfer machinery.

A 2023 review by Michaelis and Grohmann summarizes evidence that biofilms can provide favourable conditions for antibiotic-resistance gene exchange, while emphasizing the importance of experimental models for understanding the underlying processes.

The appropriate conclusion is that biofilm structure changes the conditions for horizontal gene transfer, not that every biofilm necessarily promotes gene exchange.

How does horizontal gene transfer contribute to antibiotic resistance?

Antibiotic resistance can arise through mutation or through the acquisition of resistance-associated genes.

Mobile genetic elements are particularly important because they can carry multiple genes and move between compatible bacterial hosts.

For example, a conjugative plasmid may carry genes encoding antibiotic-inactivating enzymes, altered cellular targets or efflux systems.

If the plasmid enters a suitable recipient and its resistance genes are expressed, the recipient's antibiotic susceptibility may change.

Several barriers can prevent establishment. The DNA must reach the recipient, evade degradation, replicate or integrate, and remain sufficiently stable. The acquired genes must also function in the recipient's cellular background.

Antibiotic exposure can favour bacteria carrying resistance determinants, but horizontal transfer itself does not require antibiotic selection in every experimental setting.

Research on plasmids from a One Health perspective also shows why resistance cannot be understood solely within hospitals. Genetic elements and their bacterial hosts occur across human, animal and environmental habitats.

Nevertheless, detecting the same resistance gene in different settings does not establish the direction of transfer between them.

Can microbiome sequencing prove that genes were transferred?

Microbiome sequencing can identify genetic material associated with mobile elements, resistance determinants and bacterial taxa.

It can also reveal similarities between genes or genomic regions recovered from different organisms.

However, these observations do not automatically prove that a transfer event occurred during the study.

Consider two bacterial species detected in the same faecal sample. If both contain a similar antibiotic-resistance gene, several explanations are possible.

The gene may have been acquired through an earlier horizontal transfer event. It may be carried on related mobile elements that entered the populations independently. The sequence similarity might also reflect a longer evolutionary history rather than transfer during the sampling period.

Short-read metagenomic data may additionally make it difficult to determine which bacterial chromosome or plasmid carries a particular gene.

Long-read sequencing, complete genome assemblies and careful analysis of mobile-element boundaries can improve genetic context.

For stronger evidence of active transfer, researchers may use experimental donor–recipient systems, isolate transconjugants, track genetic markers or compare genomic changes across controlled conditions.

Even then, the result should be interpreted within the experimental system.

A detected resistance gene is not equivalent to a demonstrated resistant phenotype, and a predicted conjugative element is not equivalent to an observed conjugation event.

Comparing the three mechanisms

On a phone, swipe the table left or right to view all three mechanisms.

These categories are useful for learning, but bacterial genetic exchange is more diverse than a simple three-column diagram suggests. Mobile elements can depend on one another, and the environment can change how efficiently the mechanisms operate.

For related background, read our articles on Bacteria: Their Characteristics, Diversity and Roles in Nature, Escherichia coli: Types, Habitats and Current Research and Bacteriophage Therapy.

What should students and researchers remember?

Horizontal gene transfer is one of the processes that allow bacterial populations to acquire genetic variation beyond that produced by mutation.

Transformation, transduction and conjugation differ in their routes of DNA transfer, but all depend on molecular compatibility and successful establishment of the incoming genetic material.

Recent studies have added important detail to the classical explanations. Natural transformation involves coordinated DNA-processing proteins. Conjugation efficiency differs greatly among plasmids and environments. Chromosomal mobile elements can contribute substantially to genetic variation, even in bacteria without plasmids. Bacteriophages can also influence conjugation indirectly by changing how bacterial populations grow together.

Finding a gene, predicting that it can move and directly observing its transfer are three different levels of evidence.

Recognizing that distinction helps microbiologists interpret bacterial genomes, antimicrobial-resistance studies and microbiome datasets without claiming more than the evidence supports.

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