22 July 2016

Kamikaze bacteria fight cancer

Julia Korowski, XXII CENTURY, based on EurekAlert! – Synthetic biology used to limit bacterial growth and coordinate drug release

Scientists at the University of California at San Diego (University of California, San Diego) and the Massachusetts Institute of Technology (Massachusetts Institute of Technology) have bred microorganisms capable of producing anti-cancer drugs. Once in the body, the bacteria self-destruct and secrete the drug into the tumor area. The new method combined with chemotherapy extended the life of laboratory mice by 50%. The results of the study are published in the journal Nature (Din et al., Synchronized cycles of bacterial lysis for in vivo delivery).

"One of the goals of treatment in synthetic biology is to work with foci of the disease and minimize damage. In addition, we wanted to deliver a significant drug load to the affected area," explains Jeff Hasty, one of the authors of the study. The prospect of using bacteria to deliver drugs is tempting, since they can populate hard-to-reach areas of the tumor where traditional chemotherapy "does not reach".

The researchers created three bacterial strains. In the microorganisms of each line, they embedded a gene responsible for the production of antitumor protein, and a gene that triggers the process of self-destruction (lysis). Each strain produced one of the medicinal substances, and during the experiments, scientists found out that the combination of all three proteins works most effectively. In order for the drugs to suppress tumor growth, it was necessary to control the reproduction of bacteria and maintain their population at the right level. To do this, scientists used the natural ability of microorganisms to coordinate their behavior – a sense of quorum.

Quorum sensing is the ability of some bacteria to communicate and coordinate behavior through the secretion of molecular signals. For example, opportunistic pathogenic bacteria Pseudomonas aeruginosa can make general decisions to adapt to the peculiarities of the environment and their own protection. This makes them particularly resistant even to large doses of antibiotics. The biofilm formed by bacteria protects the whole colony from harmful substances, including antibiotics, entering it.

Bacteria of new strains secrete a signaling molecule AHL (N-Acyl homoserine lactones, N-acyl-homoserylactone), which moves between cells and "turns on" the necessary genes, including those that regulate the synthesis of the molecule itself. Microorganisms begin to produce medicine, and produce AHL, over time, AHL becomes more and more, and when its concentration exceeds the permissible limit, the bacteria self-destruct and secrete antitumor substances into the body. The surviving cells begin to divide again, and the process repeats.

After tests on HeLa cell lines demonstrated that the proteins produced by microorganisms actually kill cancer cells, scientists began experiments on laboratory animals. Experiments have shown that the combination of bacterial and chemotherapy more effectively inhibits the growth of tumors in mice than any of the methods separately. However, the researchers note that it was not possible to cure the animals using the new approach. The combination of drugs and bacteria prolonged the life of mice by 50%, but how this treatment would affect humans is unknown.

The main thing that scientists have managed to achieve is to show that the new treatment method can really work. "Combination therapy does not lead to the destruction of the tumor," states Shibin Zhou, an employee of Johns Hopkins University, who did not participate in the study. – But the idea of developing such bacterial chains is very progressive. It shows that this concept is workable, and it can be used to treat not only cancers."

Portal "Eternal youth" http://vechnayamolodost.ru  22.07.2016

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