Background & Inspiration

Antibiotic Resisitance

Since antibiotics were put into use in the early 20th century , they have saved billions of lives from lethal infection. Nevertheless, the rising risk of severe side-effects and the potential antibiotic resistance limit the usage of antibiotics. According to a 2019 report from US Department of Health and Human Services, more than 2.8 million antibiotic-resistant infections occur in the U.S. each year, and more than 35,000 people die as a result[1].

Antibiotics resistance has a long history, which is just began short after the commercialization of antibiotic. Here is a list of antibiotic resistant germs over time from CDC’s site.

Antibiotic Approved or Released	Year Released	Resistant Germ Identified	Year Identified
Penicillin	1941	Penicillin-resistant Staphylococcus aureus Penicillin-resistant Streptococcus pneumoniae Penicillinase-producing Neisseria gonorrhoeae	1942 1967 1976
Vancomycin	1958	Plasmid-mediated vancomycin-resistant Enterococcus faecium Vancomycin-resistant Staphylococcus aureus	1988 2002
Amphotericin B	1959	Amphotericin B-resistant Candida auris	2016
Methicillin	1960	Methicillin-resistant Staphylococcus aureus	1960
Extended-spectrum cephalosporins	1980 (Cefotaxime)	Extended-spectrum beta-lactamase- producing Escherichia coli	1983
Azithromycin	1980	Azithromycin-resistant Neisseria gonorrhoeae	2011
Imipenem	1985	Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae	1996
Ciprofloxacin	1987	Ciprofloxacin-resistant Neisseria gonorrhoeae	2007
Fluconazole	1990 (FDA approved)	Fluconazole-resistant Candida	1988
Caspofungin	2001	Caspofungin-resistant Candida	2004
Daptomycin	2003	Daptomycin-resistant methicillin-resistant Staphylococcus aureus	2004
Ceftazidime-avibactam	2015	Ceftazidime-avibactam-resistant KPC-producing Klebsiella pneumoniae	2015

The history of antibiotic resisitance[2]

Antibiotics resistance develops fast. It’s nearly inevitable due to the evolution pressure from the application of antibiotics. Among the several ways to tackle the antibiotics resistance, developing new drug is the most promising one.

Saving Firefighters from Bushfire

As a fire-prone state, wildfire has burned 3.9 millions land in California this year, which is the forth fire this three years. Across the state, 17,000 firefighters are fighting with nearly 24 fire. Wild fires frequently occur in Australia during the hot and dry season. From November 8 last year to February 13 this year, the fire lasted for four months, which caused at least 33 death, mostly are firefighters, and many firefighters from other countries dead. In Liangshan County, Sichuan Province, due to the continuous forest fires in the spring of 2019 and 2020, people have endured a lot. To put out the fire, we sacrificed 31 firefighters and a large number of personnel. ire leads to plenty of loss and casualities all around the world annaully. Firefighters are easier to get burnt or bruised in their daily training or working. The risk of infection is high if those wounds are not treated in time. To protect our firefighters from lethal bacterial infection, we intend to develop an antibacterial and completely biodegradable adhesive bandage.

Our Solution

Antimicrobial peptides (AMPs)

Antimicrobial peptides (AMPs) are small peptides which are anti-bacterial, anti-viral, anti-microbial, anti-protozoal, even anti-cancer. As parts of innate immunity, AMPs are produced by all known living species (ranging from bacteria, fungi, and plants to invertebrates, non-mammalian vertebrates, and mammals).

Compared to antibiotics, AMP activity does not lead to a mutation-inducing SOS response which could cause antibiotics resistance.[3]

What’s more? AMPs also promote tissue healing and exhibit broad spectrum antibacterial activity. Its wide biological activity displays the bright future in Biomedical Science. Besides, it has low toxicity, which shows that AMPs have less risks when we use them.

Polyhydroxyalkanoates (PHA)

Polyhydroxyalkanoates (PHA) are a diverse biopolyesters synthesized by many bacterial. Besides, PHA materials have been produced in large quantity for various application research including medical implants for about 30 years. Moreover, common PHA biodegradation products including oligomers and monomers are also not toxic to the cells and tissues compatible properties. Importantly, pharmaceutical applications of some PHA degradation products also have been reported. As a result, PHA has bright application potential in synthetic biology field.

Polyhydroxyalkanoates surface binding protein (PhaP)

PhaP is an amphiphilic protein which can attach to the surface of PHA particles. It has a hydrophilic domain and a hydrophobic domain. The hydrophobic domain can interact with various types of hydrophobic surfaces. In that case, if a protein can bind to PhaP, then it can link to hydrophobic surfaces by PHAs and PhaP indirectly.

The method we use to combine PhaP and AMP is a gene-level fusion mediated by a flexible linker peptide. The linker with low hydrophobicity and low charge effect can stretch fully to separate the different fusion components on both sides, so that PhaP and AMP will fold to their natural conformations without interfering with each other. In that case, we can use synthetic biology tool to produce our product.

Project Goal

In the laboratory, we aimed to prove that the complex expressed by engineering bacteria has inhibitory effect on Staphylococcus aureus. In the real world, we are going to set up a company to produce our products. We are now applying for a patent in these days.

COVID-19 Impact

Since the end of 2019, the Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) spread to all world, which made the whole world suffered. The epidemic influenced us a lot.

As for the experiment part of our project, it shortened our experiment time greatly. We were supposed to come back to campus in February 9th, 2020 and continued brainstorm to construct the project. As a result of epidemic, we had to start brainstorm online. It was surprised that we determined our project in April 10th but still have no solution for starting the experiment. The only thing we could do was searching for many literatures to improve the success rate of the experiment. Finally, we came back to school at August 23 rd and started our experiment as soon as possible.

Viewing from the online Giant Jamboree and the CCiC (Conference of China iGEMer Community), compared with the former Giant Jamboree and the CCiC, we didn’t have the opportunity to communicate with superior teams all over the world face to face. And the presentation on line is not as clear as face to face. Sometimes, it was influenced by all participants’ Net situations.

The epidemic also influenced the mentality of all team members sometimes. We were looking forward to coming back to campus from February 9th to August 23rd. During that period, we had no choices but to encourage each other but still didn’t have the confidence about the experiment part of our project.

All in all, we have learned a lot this year. We received many useful suggestions about our project on modeling, human practice etc. We would like to thank people who helped us and we hope that our friendship could keep going on.

Reference

[1] Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Healthcare June 18, 2020, United Nations, accessed 27 October

[2] Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Healthcare March 13, 2020, United Nations, accessed 27 October

[3] Probiotics Antimicrob Proteins. 2019 Jun;11(2):370-381. doi: 10.1007/s12602-018-9465-0. PMID: 30229514 Review.

Team:NWU-CHINA-A/Description