Thermoregulated microbes have learned to deliver medicines
Sofia Dolotovskaya, N+1
Scientists from the California Institute of Technology (Caltech) have developed bioengineered bacteria that respond to temperature changes by changing gene expression. Such bacteria can be used in the future for controlled delivery and release of drugs in any part of the body. The article was published in the journal Nature Chemical Biology (Piraner et al., Tunable thermal bioswitches for in vivo control of microbial therapeutics).
Recently, there are more and more methods of microbial therapy – the use of bioengineered bacteria in medicine. One of the important areas of microbial therapy is the delivery of medicines with the help of bacteria. However, the main disadvantage of such delivery methods is that the bacteria cannot be controlled. Meanwhile, ideally, bacteria should not only be directed to a specific place in the body, but also be able to "turn on" them at the right time. The authors decided to use temperature as a method of control.
To do this, the authors used two transcription regulators that change their activity in response to temperature changes. The first is the TlpA protein of the bacterium Salmonella typhimurium, and the second is the protein of the bacteriophage virus λ (phage lambda) cI. Both of these proteins bind to DNA and regulate gene expression depending on temperature.
Scientists applied "directed evolution" to these proteins, a method of protein engineering that allows choosing the right ones from a variety of variants obtained by mutagenesis. Using this method, the authors "adjusted" the temperatures to which the proteins react. For example, salmonella protein was initially activated in the temperature range from 42 to 44 degrees. The authors also created a version of the protein that is activated at temperatures from 36 to 39 degrees. Then the genes encoding these bioengineered proteins were embedded in the genome of the common Escherichia coli Escherichia coli.
Drawings from the press release of Caltech Biologists Give Bacteria Thermostat Controls - VM
The theoretical possibilities for the use of such thermoregulated bacteria in scientific research and in medicine are very wide. The authors, using mice, successfully tested three possible applications in vivo. The first option is that the bacteria expressing a certain conditional drug were "ordered" to release this drug only in a certain area of the patient's body (in this case, mice) and nowhere else. To do this, scientists simply heated this part of the body with ultrasound (this is a very soft method that allows you to heat crumbled tissue areas with an accuracy of a millimeter). In the second application, the bacteria were programmed to stop the delivery of the drug at the right moment or even self-destruct when the patient's temperature rises to certain values. This is necessary to stop therapy in the event that it did not work (that is, when the patient developed a high fever).
In the third experiment, the authors demonstrated that, in addition to medical advantages, thermoregulated bacteria can also be endowed with environmental properties. The researchers programmed the bacteria to self-destruct after they leave the patient's body during defecation and enter an environment with a lower temperature. In this way, it will be possible to prevent a large number of bioengineered bacteria from entering the environment.
In previous studies, scientists have shown that some bacteria naturally move to tumors because they prefer hypoxic (low-oxygen) conditions. Such bacteria can be used to deliver drugs directly to hypoxic areas of tumors. In other studies, bacteria have been tested to deliver drugs that reduce inflammation to the intestine. And in one study, diatoms were even used to deliver drugs to tumors.
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16.11.2016