Genetically modified bacteria

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Genetically modified bacteria were the first organisms to be modified in the laboratory, due to their simple genetics.[1] These organisms are now used for several purposes, and are particularly important in producing large amounts of pure human proteins for use in medicine.[2]

History

The first example of this occurred in 1978 when

U.S. Food and Drug Administration
.

Research

Left: Bacteria transformed with pGLO under ambient light Right: Bacteria transformed with pGLO visualised under ultraviolet light

Bacteria were the first organisms to be genetically modified in the laboratory, due to the relative ease of modifying their chromosomes.[3] This ease made them important tools for the creation of other GMOs. Genes and other genetic information from a wide range of organisms can be added to a plasmid and inserted into bacteria for storage and modification. Bacteria are cheap, easy to grow, clonal, multiply quickly, are relatively easy to transform, and can be stored at -80 °C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria, providing an unlimited supply for research.[4] The large number of custom plasmids make manipulating DNA excised from bacteria relatively easy.[5]

Their ease of use has made them great tools for scientists looking to study gene function and

nucleotides.[8][9][10]

Food

Bacteria have been used in the production of food for a very long time, and specific strains have been developed and selected for that work on an industrial scale. They can be used to produce

alpha-amylase, which converts starch to simple sugars, chymosin, which clots milk protein for cheese making, and pectinesterase, which improves fruit juice clarity.[12]

In cheese

Chymosin is an enzyme produced in the stomach of young ruminant mammals to digest milk. The digestion of milk proteins via enzymes is essential to cheesemaking. The species Escherichia coli and Bacillus subtilis can be genetically engineered to synthesise and excrete chymosin,[13] providing a more efficient means of production. The use of bacteria to synthesise chymosin also provides a vegetarian method of cheesemaking, as previously, young ruminants (typically calves) had to be slaughtered to extract the enzyme from the stomach lining.

Industrial

Genetically modified bacteria are used to produce large amounts of proteins for industrial use. Generally the bacteria are grown to a large volume before the gene encoding the protein is activated. The bacteria are then harvested and the desired protein purified from them.[14] The high cost of extraction and purification has meant that only high value products have been produced at an industrial scale.[15]

Pharmaceutical production

The majority of the industrial products from bacteria are human proteins for use in medicine.[16] Many of these proteins are impossible or difficult to obtain via natural methods and they are less likely to be contaminated with pathogens, making them safer.[14] Prior to recombinant protein products, several treatments were derived from cadavers or other donated body fluids and could transmit diseases.[17] Indeed, transfusion of blood products had previously led to unintentional infection of haemophiliacs with HIV or hepatitis C; similarly, treatment with human growth hormone derived from cadaver pituitary glands may have led to outbreaks of Creutzfeldt–Jakob disease.[17][18]

The first medicinal use of GM bacteria was to produce the protein

tissue plasminogen activator which dissolves blood clots.[14] Outside of medicine they have been used to produce biofuels.[23] There is interest in developing an extracellular expression system within the bacteria to reduce costs and make the production of more products economical.[15]

Health

With greater understanding of the role that the

enzymes or proteins. One research focus is to modify Lactobacillus, bacteria that naturally provide some protection against HIV, with genes that will further enhance this protection.[24] The bacteria which generally cause tooth decay have been engineered to no longer produce tooth-corroding lactic acid.[25] These transgenic bacteria, if allowed to colonize a person's mouth, could perhaps reduce the formation of cavities.[26] Transgenic microbes have also been used in recent research to kill or hinder tumors, and to fight Crohn's disease.[27]

If the bacteria do not form

colonies
inside the patient, the person must repeatedly ingest the modified bacteria in order to get the required doses. Enabling the bacteria to form a colony could provide a more long-term solution, but could also raise safety concerns as interactions between bacteria and the human body are less well understood than with traditional drugs.

One example of such an intermediate, which only forms short-term colonies in the

Lactose Intolerance. This genetically modified version of Lactobacillus acidophilus bacteria produces a missing enzyme called lactase which is used for the digestion of lactose found in dairy products or, more commonly, in food prepared with dairy products. The short term colony is induced over a one-week, 21-pill treatment regimen, after which, the temporary colony can produce lactase
for three months or more before it is removed from the body by a natural processes. The induction regimen can be repeated as often as necessary to maintain protection from the symptoms of lactose intolerance, or discontinued with no consequences, except the return of the original symptoms.

There are concerns that horizontal gene transfer to other bacteria could have unknown effects. As of 2018 there are clinical trials underway testing the efficacy and safety of these treatments.[24]

Agriculture

For over a century bacteria have been used in agriculture. Crops have been

ice crystals around themselves. This led to the development of ice-minus bacteria, that have the ice-forming genes removed. When applied to crops they can compete with the ice-plus bacteria and confer some frost resistance.[28]

This artwork is made with bacteria modified to express 8 different colours of fluorescent proteins.

Other uses

Other uses for genetically modified bacteria include bioremediation, where the bacteria are used to convert pollutants into a less toxic form. Genetic engineering can increase the levels of the enzymes used to degrade a toxin or to make the bacteria more stable under environmental conditions.[29] GM bacteria have also been developed to leach copper from ore,[30] clean up mercury pollution[31] and detect arsenic in drinking water.[32] Bioart has also been created using genetically modified bacteria. In the 1980s artist Joe Davis and geneticist Dana Boyd converted the Germanic symbol for femininity (ᛉ) into binary code and then into a DNA sequence, which was then expressed in Escherichia coli.[33] This was taken a step further in 2012, when a whole book was encoded onto DNA.[34] Paintings have also been produced using bacteria transformed with fluorescent proteins.[33][35][36]

Bacteria-synthesized transgenic products

References

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  4. ^ "Rediscovering Biology - Online Textbook: Unit 13 Genetically Modified Organisms". www.learner.org. Archived from the original on 2019-12-03. Retrieved 2017-08-18.
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  6. ^ Cooper GM (2000). "Cells As Experimental Models". The Cell: A Molecular Approach. 2nd Edition.
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  22. ^ Summers, Rebecca (24 April 2013) "Bacteria churn out first ever petrol-like biofuel" New Scientist, Retrieved 27 April 2013
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  29. ^ Valda D, Dowling J (10 December 2010). "Making Microbes Better Miners". Business Chile Magazine. Archived from the original on 17 December 2010. Retrieved 21 March 2012.
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  31. ^ Sanderson K (24 February 2012). "New Portable Kit Detects Arsenic In Wells". Chemical and Engineering News.
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  33. ^ Agapakis C. "Communicating with Aliens through DNA". Scientific American Blog Network. Retrieved 2018-09-13.
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Further reading