Team:UCAS/Description
Description
"Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistant" [1]. This is a warning given by Alexander Fleming, who discovered the very first antibiotic, penicillin, when collecting his Nobel Prize in 1945. Now more than 70 years has passed, there have been hundreds kinds of antibiotics readily available to most people. However, the mass production and misuse of antibiotics make them detectable in many places besides hospitals.
The mass production and abuse of antibiotics
Since penicillin was invented in 1928, antibiotics have been massively produced and have saved millions of people. However, the relatively low price of antibiotics has also led to its misuse, especially in developing countries like China.
In China, about 147,000 tonnes of antibiotics are produced annually. Also, antibiotics are often overused in hospitals, livestock farms and fish farms. Waste water from above facilities is emitted to rivers without proper treatment. Thus the rivers are heavily polluted by antibiotic residues.
Our survey indicates that people have misunderstandings on the correct use of antibiotics. Out-of-date antibiotic drugs are disposed randomly which is adding to the antibiotic residue pollution.
It is believed that high antibiotic residue concentration in natural environment reinforces the spread of resistant genes. In order to tackle the resistant bacteria, more antibiotic drugs should be taken so the resistant gene will be even stronger. And at the end of this vicious cycle, drugs we use today will no more be cures tomorrow.
Among all kinds of antibiotics, tetracycline is one of the most produced and used. Besides, it is hard for tetracycline to degrade in natural condition. And that is why it is one of the most resistant antibiotics.
The emerging problem of antibiotic residues
Antibiotic residues, which we denote as AR later, are almost everywhere around us, yet the public is not aware of it. AR have been detected in honey, milk, meats, as well as in plants, surface water and sediments, to number a few, which medicine, animal feed and pesticides. Nonetheless, the scale of AR in China was not studied until recently, which then turned out that some 53,800 tonnes of antibiotics enter natural environment from waste water treatment plants annually [2].As for the effect of AR on human health, some researches has suggested that it could lead to obesity [3], Some antibiotics can lead to toxic damage, allergic reaction, carcinogenic effect, mutagenic effect, etc. High concentration of antibiotic residues in environment also encourages antibiotic resistance, since AR exposure is a form of “underdose” as Fleming has mentioned.
Stunned by the large amount of antibiotic residues in Chinese urban rivers [4], UCAS iGEM team is devoted to degrading antibiotic residues in waste water treatment plants (WWTPs) or hospitals.
Fig. 1
Map of China showing the total antibiotic emission in each river basin [4].
During the course of paper research, we found tetracycline antibiotics is one type of the most abundant antibiotics found in urban rivers, as illustrated in the table below [5]. So we decided to focus on the degradation of tetracycline antibiotics residues.
Fig. 2
The concentrations of the target antibiotics in (a) water samples and (b) sediment samples from the Huangpu River, Shanghai, China in July 2012 [5].
Tetracycline antibiotics
Tetracycline antibiotics are protein synthesis and cell growth inhibitors, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. They do so mainly by binding to the 30S ribosomal subunit in the mRNA translation complex. [6]
Tetracycline antibiotics can inhibit the development of children's teeth and bone growth, and are also easy to cause allergic reactions. One of the most serious damage tetracycline antibiotics have exerted on human beings is the tetracycline pigmentation teeth, which is rather prevalent in China. Some cases of tetracycline pigmentation teeth have been speculated to have correlation with high concentration of tetracycline residues in drinking water.
Nowadays, tetracycline antibiotic residues mostly come from the overuse in animal husbandry and aquaculture industry. Those tetracycline antibiotics not absorbed by animals will end up in soil and water, and eventually taken in by humans.
Our team is determined to work on the degradation of tetracycline antibiotics in our surroundings. TetX monoxygenase is used as an EFFICIENT tetracycline degrading enzyme, whilst the design of a biosensor with a T7 RNA polymerase makes the system SMARTER. However, the degrading super hero in the wrong place will be superbugs. Overgrowth of these microorganisms may facilitate resistance gene transfer. In order to prevent plasmid transfer, we designed a kill switch based on Toxin-Antitoxin module to make it SAFER. Also, by controlling the information flow within the cells through our circuit design, our engineered bacteria will not express degrading enzymes unless antibiotic is presented.
We are proud to call this system Ultra-sensitive Controllable Antibiotic Scavenger: UCAS.
References
[1]http://www.nobelprize.org/nobel_prizes/medicine/laureates/1945/fleming-lecture.pdf
[2] Zhang, Q.-Q., Ying, G.-G., Pan, C.-G., Liu, Y.-S. & Zhao, J.-L. Comprehensive Evaluation of Antibiotics Emission and Fate in the River Basins of China: Source Analysis, Multimedia Modeling, and Linkage to Bacterial Resistance. Environ. Sci. Technol. 49, 6772–6782 (2015).
[3] Pool, R. The Interplay Between Environmental Chemical Exposures and Obesity. (2016).
[4]Zhang, Q.-Q., Ying, G.-G., Pan, C.-G., Liu, Y.-S. & Zhao, J.-L. Comprehensive Evaluation of Antibiotics Emission and Fate in the River Basins of China: Source Analysis, Multimedia Modeling, and Linkage to Bacterial Resistance. Environ. Sci. Technol. 49, 6772–6782 (2015).
[5] K. Chen, J.L. Zhou. Occurrence and behavior of antibiotics in water and sediments from the Huangpu River, Shanghai, China. Chemosphere, 95, 604–612 (2014)
[6] Tetracycline antibiotics - Wikipedia https://en.wikipedia.org/wiki/Tetracycline_antibiotics
