Here at Addgene, we often refer to plasmids as lab or experimental tools. They certainly are very handy in research, but we’re really borrowing these tools from Mother Nature’s toolbox. Natural plasmids, also called environmental plasmids, are all around us!
A plasmid is a small piece of DNA that can replicate independently from its host’s chromosome. Although we usually think of bacteria when we think of plasmids, both Archaea and Eukaryota can also harbor these circular DNA passengers.
Most natural plasmids encode beneficial traits to entice their hosts to keep them around and even help them spread. They can be inherited by daughter cells during cellular reproduction, similar to the host’s chromosome, or they can spread between hosts through horizontal (or “lateral”) gene transfer. Horizontal gene transfer can occur naturally through transformation (cellular uptake from the environment), transduction (viral infection by bacteriophages), or conjugation (direct transfer from one cell to another). Bacteria need special fertility genes to be capable of conjugation, and these are encoded by certain kinds of plasmids — more on that in a minute!
Fun fact! Electroporation is one popular method scientists use to promote transformation, but it isn’t just for lab specimens — there is evidence that lightning can also promote gene transfer in soil bacteria! (Demanèche et al., 2001)
Beneficial traits of natural plasmids
Natural plasmids often convey a variety of functions that allow their host organisms to thrive in competitive environments. The genes encoding these functions form the basis of many molecular biology tools!
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| Figure 1: Common functions of natural plasmids. Created with BioRender.com. |
Resistance (R) plasmids: microbial defense
Genes allowing bacteria to survive toxins are the clearest example of a plasmid benefiting its host. For example, cells with a penicillin resistance plasmid can grow in spite of a hostile Penicillium fungus trying to kill them off.
While antibiotic resistance-mediated selection is indispensable for cloning work, antibiotics and plasmid-encoded resistance to them are the tools of a millennia-old microbial war that humans only noticed last century! Nevertheless, the transfer of plasmids carrying these genes between bacteria can also have serious implications for public health.
Bacteriocin plasmids: microbial offense
One way to triumph over your neighbors is to eliminate the competition, and Penicillium isn’t the only organism that knows it. Some bacteria possess plasmid-borne toxins like colicins and subtilisins to kill other bacteria in the area, freeing up resources for themselves. Conveniently, plasmids carrying genes for bacterial toxins like colicin typically also carry the necessary resistance genes to help cells survive their own secretions.
Pro tip! Historically, colicin-producing plasmids have been referred to as “Col plasmids” or “Col factors.”
Virulence plasmids: microbial infection
Virulence plasmids encode genes that allow the host to infect other organisms. If you’ve ever wondered why E. coli is safe to use in the lab but also causes outbreaks of food poisoning, the difference is virulence plasmids! This category includes genes that help bacteria invade hosts, including attaching to host cells and evading the host immune system, and those that produce toxins that cause disease. While these plasmids can be dangerous, they also provide researchers with new means to deliver DNA and other molecules to host organisms. For instance, vectors derived from the Agrobacterium Ti virulence plasmid are now used routinely in biotechnology to transform plant cells.
Degradative plasmids: microbial hardiness
There are also less aggressive ways to survive in competitive environments — like by living where no one else wants to. Some organisms manage this with plasmids that allow them to eat unusual substrates that other organisms can’t use. Other plasmids offer resistance to toxic substances like heavy metals or pesticides, enabling their hosts to survive where others can’t. This ability to endure a harsh environment is distinct from the benefit of resistance plasmids, which protect the host from attacks by other organisms.
To conserve energy, these specialized degradative capabilities are often tightly regulated to be active only in the presence of the target compound. These systems are a gold mine of parts for synthetic biology, especially when combined with natural inducible expression systems that allow tuning of metabolic pathways.
Fertility (F) plasmids: microbial sharing
F plasmids contain the genes for bacteria to form a sex pilus, a “bridge” of cytoplasm that allows a donor cell to transfer genetic material to a recipient through direct contact. That’s conjugation! F factors can also be integrated into the bacterial chromosome, but when encoded on plasmids, they can promote rapid spreading of genetic material through a population of cells.
Cryptic plasmids: microbial mysteries
Cryptid hunters watch out — cryptic plasmids are real! This term refers to plasmids that don’t have known functions. While some of these plasmids likely have undiscovered functions, many are simply genetic parasites. Cryptic plasmids tend to be small and poorly studied, but some researchers have suggested they may have relevance to human health (Fogarty et al., 2024), and others have proposed developing new cloning techniques based on these vectors (Shareck et al., 2004).
Plasmid categorization is complex
Plasmid classification has shifted over the years, and new classifications are still being created as whole-genome sequencing becomes more relevant (Garcillán-Barcia et al., 2023). In this post, we’ve grouped plasmids based on the phenotype they offer their host cell, but this functional organization doesn’t necessarily reflect genetic relationships or plasmid incompatibility.
Plasmids may also have more than one function: for example, Gateway cloning relies on genes found on an E. coli fertility plasmid that also encodes a toxin, CcdB, and the resistance to that toxin, CcdA. Knowing which strains of E. coli contain this F plasmid is critical for successful Gateway cloning.
In addition, scientists have engineered entirely new types of plasmids without clear analogues in nature. For example, helper plasmids were developed to replace helper viruses in AAV production systems.
We’re just skimming the surface of the natural plasmid world in this post. The great diversity of natural plasmids and their functions has enabled researchers to develop and deposit the many plasmid tools available in the Addgene repository. To learn more about some other common plasmid features, such as origins of replication and promoters, check out our other Plasmids 101 posts, and keep an eye on the Addgene blog as scientists continue to explore Mother Nature’s toolbox for new and exciting molecular technologies!
This post was originally written by Jessica Welch in January 2017 and was updated by Emily P. Bentley in October 2024.
References and Resources
References
Demanèche, S., Bertolla, F., Buret, F., Nalin, R., Sailland, A., Auriol, P., Vogel, T. M., & Simonet, P. (2001). Laboratory-scale evidence for lightning-mediated gene transfer in soil. Applied and Environmental Microbiology, 67(8), 3440–3444. https://doi.org/10.1128/AEM.67.8.3440-3444.2001
Fogarty, E. C., Schechter, M. S., Lolans, K., Sheahan, M. L., Veseli, I., Moore, R. M., Kiefl, E., Moody, T., Rice, P. A., Yu, M. K., Mimee, M., Chang, E. B., Ruscheweyh, H.-J., Sunagawa, S., Mclellan, S. L., Willis, A. D., Comstock, L. E., & Eren, A. M. (2024). A cryptic plasmid is among the most numerous genetic elements in the human gut. Cell, 187(5), 1206-1222.e16. https://doi.org/10.1016/j.cell.2024.01.039
Garcillán-Barcia, M. P., Redondo-Salvo, S., & de la Cruz, F. (2023). Plasmid classifications. Plasmid, 126, 102684. https://doi.org/10.1016/j.plasmid.2023.102684
Shareck, J., Choi, Y., Lee, B., & Miguez, C. B. (2004). Cloning Vectors Based on Cryptic Plasmids Isolated from Lactic Acid Bacteria:Their Characteristics and Potential Applications in Biotechnology. Critical Reviews in Biotechnology, 24(4), 155–208. https://doi.org/10.1080/07388550490904288
Additional Resources on the Addgene Blog
- Plasmids 101: Antibiotic Resistance Genes
- Antibiotic Resistance: An Old Solution but a New Problem
- Plasmids 101: What is a Plasmid?
- Plasmids 101: Transformation, Transduction, Bacterial Conjugation, and Transfection
Resources on Addgene.org
Addgene's Synthetic Biology Collection
Topics: Plasmids 101, Microbiology, Plasmids
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