Team:UESTC-China/Description

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Severity and Harm of Antibiotic Pollution

Severity of antibiotic pollution

As we know, antibiotics are widely applied to the treatment and prevention of diseases for human and animals, saving countless lives. It is estimated that 100,000 to 200,000 tons of antibiotics are consumed worldwide each year [1]. The abuse of antibiotics has caused serious environmental pollution. For example, in 2013, China consumed 92,700 tons of antibiotics, and 54,000 of them were excreted. Among the 54,000 tons, most (99.6％) are released into the environment [2], posing a huge threat to people and ecosystems.

Antibiotics in the water environment

Antibiotics have the most serious impact on the water environment, because most of them eventually enter the water environment. A large-scale survey of rivers in 72 countries conducted in 2019 showed that antibiotics were found at 66% of the 711 sampling sites [3]. Besides, in literature, we found examples of considerable antibiotic pollution in fresh waters. In America, antibiotic concentration of up to 15 μg/L has been measured, with higher concentration reported from European and African studies (over 10 μg/L and 50 μg/L respectively). And in Asian-Pacific countries, the concentration is over 450 μg/L [1].

Fig. 1. Antibiotics pollution worldwide [1,3]

Consequences of antibiotic pollution

Some antibiotics in water could affect microorganisms at concentration below 10 μg/L [1], inducing anti-microbial resistance (AMR). Bacteria with AMR could resist the action of the drug, and through the biological chain, it may cause potential harm to other living creatures. According to the report, current worldwide deaths attributable to AMR, including antimalarial and antiviral resistance, have been estimated at ~700,000 per year, rising to 10 million per year by 2050 if present trends continue [4,5].

How to help solve antibiotic pollution？

So we started thinking, could we do something to help solve antibiotic pollution?

Where do antibiotics come from？

First, we want to figure out where the antibiotics come from. Actually, we found that antibiotics are everywhere in our life, including rivers, soil and even air [6]. In order to know the sources of antibiotics in the environment, we visited a water purification plant in Chengdu and learned that the antibiotics in sewage mainly come from two kinds of emissions. One is in production, such as pharmaceutical wastewater, the other is in use, mainly medical antibiotics and veterinary antibiotics.

Existing methods of disposing antibiotics

Most antibiotics end up in water, but almost all conventional treatments applied in wastewater treatment plants and drinking water treatment plants (such as coagulation, flocculation, sedimentation and filtration) were unsuccessful in the removal of these compounds, therefore, some physical and chemical methods or combined processes were developed to treat antibiotics in water. Here we list three important approaches in table 1 [7].

Table 1
Existing treatments for antibiotics in water originally from the literature [7] with some modifications.
Methods	Advanced oxidation processes(AOPs)		Adsorption	Combined processes
Methods	Ozonation	Fenton oxidation	Adsorption	Combined processes
Short description	Most tested methodologies in AOP		Alternative to oxidation	AOP+Biological treatment/Membrane Adsorption
Advantages & Features	Applied to fluctuating flow rates and compositions	To treat β-lactam antibiotics	High efficiency(>80%)	Most powerful
Disadvantages	1.Hign cost 2.Require lots of energy	1.Complexity	1.Hign cost 2.Produce new pollution	1.Hign cost 2.Complexity 3.Not practical

Our solution

Antibiotic problem for expired drugs

We note that studies have shown that improper disposal of unused/expired drugs, which are directly discharged in the sewage network or deposited in landfills, can also be considered as significant points of antibiotic contamination [8,9]. However, our investigation shows that people pay little attention to expired drugs.

The Chinese Family Expired Drugs Recycling White Paper made clear that an estimated 78.6% of households in China have small family medicine kits. However, more than 80% of households have no habit of cleaning their kits regularly. As a result, there are about 15,000 tons of expired drugs appearing in China a year [10,11]. According to the survey, the most common categories of family medicines are cough and cold medicines (47.8%) and systemic antibiotics (30.0%) [12]. Many of these two kinds of medicines contain antibiotic components. Therefore, we believe that the disposal of expired drugs can decrease the pollution of antibiotics to some extent.

Fig. 2. Expired drugs in China [10-12]

In our project, we take CIP for example to build a system of degrading antibiotics with synthetic biology.

Why we chose ciprofloxacin?

Ciprofloxacin is a commonly used antibiotic in clinical practice, which is a class of quinolone antibiotics, and it has been shown that ciprofloxacin and erythromycin have the highest rates of resistance (20% to 60%) among the antimicrobial agents considered essential to human medicine [13]. A large-scale survey of rivers in several countries and regions around the world found that, the concentration of commonly prescribed drug ciprofloxacin was eight times over the safe level in the river with the highest levels of antibiotics [3]. In conclusion, ciprofloxacin is a widely used and harmful antibiotic.

CIP degradation system

We noticed that the enzyme CrpP found in 2018 has the ability to phosphorylate and thus degrade CIP [14], so we utilized CrpP CDS as a basis of CIP biodegradation pathway. Meanwhile, we added a quorum sensing system to enhance the expression of CrpP by E.coli [15]. When upstream inducible promoter is activated by CIP, quorum sensing system will facilitate downstream CrpP’s expression and degrade CIP consequently.

To use engineered bacteria more effectively, we built the expired drugs recycling and degrading device named Drug Avenger. And we performed the modeling analysis on the layout of the device to improve the utilization rate of the device.

Click here to our design

Fig. 3. Drug Avenger：Our expired drugs recycling and degrading device

Compared with other present CIP treatment methods, our biodegradation system has following advantages：

1. Low cost.
2. High sensitivity. Ciprofloxacin can be degraded even at low concentration.
3. High specificity. Degrade only specific antibiotics and avoid side effects.
4. It works under mild conditions.
5. More environmentally friendly.

How to applicate?

The whole system can be widely used in all kinds of antibiotics if switching to genes that encode proteins degrading different antibiotics.

A CIP recycling and degrading device named Drug Avenger was developed in our project for the treatment of the expired drug. This device has potential to handle antibiotic pollution in other occasions, for example, Sewage treatment plants, farms, etc.

We also performed the modeling analysis on the layout of the antibiotic-degrading device. It will be undoubtable to enhance the utilization efficiency for our device when this device will be used in the community in the near future. It can also provide some guidance for anyone who do the similar work.

Want to know more investigation about our project?

The detailed thinking of our project is presented in Human Practices. Click here to our Human Practices.

References

[1]Danner, M. C., Robertson, A., Behrends, V., & Reiss, J. (2019). Antibiotic pollution in surface fresh waters: Occurrence and effects. Sci. Total Environ., 664, 793-804.
[2]Zhang, Q. Q., Ying, G. G., Pan, C. G., Liu, Y. S., & Zhao, J. L. (2015). 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(11), 6772-6782.
[3]https://www.sciencenews.org/article/world-rivers-dangerous-levels-antibiotics.
[4]Roope, L. S. J., Smith, R. D., Pouwels, K. B., Buchanan, J., Abel, L., Eibich, P., . . . Wordsworth, S. (2019). The challenge of antimicrobial resistance: What economics can contribute. Science, 364(6435), eaau4679.
[5]Willyard, C. (2017). The drug-resistant bacteria that pose the greatest health threats. Nature, 543(7643), 15.
[6]Wang bin, zhou ying, & jiang qingwu. (2014). Environmental antibiotic pollution and its impact on human health. Chinese journal of preventive medicine, 48(6), 540-544.
[7]Homem, V., & Santos, L. (2011). Degradation and removal methods of antibiotics from aqueous matrices – A review. Journal of Environmental Management, 92(10), 2304-2347.
[8]Kumar, M., Jaiswal, S., Sodhi, K. K., Shree, P., Singh, D. K., Agrawal, P. K., & Shukla, P. (2019). Antibiotics bioremediation: Perspectives on its ecotoxicity and resistance. Environment International, 124, 448-461.
[9]Akici, A., Aydin, V., & Kiroglu, A. (2018). Assessment of the association between drug disposal practices and drug use and storage behaviors. Saudi Pharmaceutical Journal, 26(1), 7-13.
[10]http://health.people.com.cn/n1/2019/0815/c14739-31297021.html
[11]http://www.xinhuanet.com/health/2018-03/13/c_1122532216.htm
[12]Dong Haiyan. (2014). Eight adults did not clean the medicine box in time. Health Guide, 20(1), 62-62.
[13]Van Boeckel, T. P., Pires, J., Silvester, R., Zhao, C., Song, J., Criscuolo, N. G., ... & Laxminarayan, R. (2019). Global trends in antimicrobial resistance in animals in low-and middle-income countries. Science, 365(6459), eaaw1944.
[14]Chávez-Jacobo, V. M., Hernández-Ramírez, K. C., Romo-Rodríguez, P., Pérez-Gallardo, R. V., Campos-García, J., Gutiérrez-Corona, J. F., . . . Ramírez-Díaz, M. I. (2018). CrpP Is a Novel Ciprofloxacin-Modifying Enzyme Encoded by the Pseudomonas aeruginosa pUM505 Plasmid. Antimicrobial agents and chemotherapy, 62(6), e02629-02617.
[15]http://parts.igem.org/Lux?tdsourcetag=s_pctim_aiomsg