Team:XJTLU-CHINA/HP/Gold Integrated
HP Gold
Activity: Questionnaire Survey
In China, overuse of antibiotics is a severe problem. The alarming data shows that China has become one of the world’s top antibiotics consuming countries, with an annual per-capita consumption of antibiotics at 138 grams, or 10 times that of an average American (The Nation, 2013). The overuse of antibiotics is not only driven by physicians, but also by patients themselves. Patients frequently ask for prescribing antibiotics for some common conditions, for example, diarrhea, and sometimes even fall out with their physicians over the use of antibiotics. Patients who like to self-medicate purchase inappropriate antibiotics over the counter in pharmacies easily.
Therefore, with an aim to figure out patients’ perception of medical treatment and to improve our project design by making it more applicable so that it can handle real life problems, we conducted a public survey to better understand how bacterial enteritis are treated in daily life as well as the current situations of antibiotic overuse.
150 people had participated in the public survey, and their age ranges from 16 to 50 and the gender of the participants is relatively equal, making the statistical data relatively effective and reliable. According to the survey (Figure 1), only 25% of the patients with serious diarrhea caused by Staphylococcus aureus infection choose to go to hospital while the others just take some medicine by themselves.
For patients who take medicine by themselves, over 50% of them will take antibiotics as their first choice, Smecta being the second. This phenomenon revealed a widespread use of antibiotics in daily enteritis treatment, which may not be a wise option due to a series of side effects and the well-known existence of antibiotic resistance.
In addition to investigating the current condition of antibiotic overuse, we also asked what other measures people will take to prevent such diseases. For the majority of people, suggested by the data above, they tend to take yogurts as a preventive solution rather than Chinese medicine, giving us some clues to our project design. It is likely for us to insert the gene of antimicrobial peptides into a certain kind of probiotics. Thereafter, the genetically modified probiotics can be made into a daily yogurt product that can later be manufactured, which is likely to benefit thousands of patients who suffer from serious bacterial enteritis.
Activity: Visit to Nanjing General Hospital
China has a higher rate of antibiotic use and abuse than many western countries. One of the most dangerous potential consequences of rampant antibiotic abuse is the rapid rise of antibiotic-resistant “superbugs”, methicillin-resistant Staphylococcus aureus (MRSA) for example, that can turn into a global health issue. Hence, to figure out the real situation of antibiotic use in clinical practices and to better understand gastrointestinal diseases and their treatments, on the 28th of June, we invited an expert Ms. Hui Shi from the Department of Gastroenterology & Hepatology in Nanjing General Hospital to conduct a field investigation on the situation of antibiotic abuse, colonization of bacteria in the intestine and the universal treatment of gastrointestinal diseases.
In accordance with Ms. Shi’s words, the abuse of antibiotics in China, though has been improved a lot, yet still not negligible. Just in the case of Nanjing General Hospital, the patients can be treated with antibiotics only after getting doctors’ prescription. Fortunately, we got the data concerning the use of antibiotics from the survey and showed below:
From the survey, the most common intervention was rehydration therapy (62%) and the most common drugs are antibiotics (61%), which is followed by dioctahedral smectite (59%), probiotics (48%) and herbal medicine (32%). Therefore, this shows that there exists an extreme misuse of antibiotics in the clinic and this data also serves as a reminder that nationwide education in the rational use of antibiotics is essential.
In addition, Ms. Shi shared with us the stories about the antibiotic resistant Staphylococcus aureus. In the early 1940s, the introduction of penicillin in staphylococcal infection dramatically improved the cure of patients. However, a few years later, penicillin-resistant staphylococci were recognized, first in hospitals and subsequently in the community. By the end of 1960s, more than 80% of both community and hospital-acquired staphylococcal isolates were resistant to penicillin. Thereafter, methicillin, a penicillinase-resistant semisynthetic penicillin, was introduced. However, in less than 1 year later, methicillin-resistant S. aureus (MRSA) was reported and subsequently spread to the other parts of the world. In the 1980s, quinolones represented a significant therapeutic advancement in the treatment of patient with infection caused by S. aureus. However, quinolone resistance among S. aureus emerged quickly, more prominently than the MRSA, and became a serious clinical problem. “Therefore, if you can really use antimicrobial peptides to replace antibiotics,” said Ms. Shi, “I think it sheds light on relieving the trend that Staphylococcus aureus develops resistance to the last therapeutic resorts for fighting S. aureus infection.”
Ms. Shi also mentioned that beside the abuse of antibiotics, acute watery diarrhea, or even with blood for up to dozens of times during one day, is a very serious symptom of S. aureus infection. Diarrhea may persist for more than 14 days. And if it is MRSA infection, it may lead to pseudomembranous colitis and becomes lethal if the patients are untreated. Despite of the improvements in public health and economic wealth, the incidence of S. aureus intestinal infection still remains high and continues to be an important clinical problem.
The doctor additionally mentioned other regular methods of diagnosis of enteric infection and treatment. Initially, doctors should incubate a little sample from patients’ defecation into multiple media to identify the strain of the pathogenic bacteria that makes the patients ill. The whole diagnosis process may take a week, or if fortunately, four days at least. Therefore, it is a considerably high risk for patients who have acute diarrhea. For the treatment part, doctors usually test the tolerance of morbigenous bacteria to distinct antibiotics. At last, they prescribe the most effective antibiotic or a combination of several antibiotics to cure the illness. After this, due to the killing effects on the enteric microbial flora, post-treatment recovery is to let the patients ingest pills which are full of dry bacteria such as Bifidobacteria. In sum, the whole therapy costs more than one week. Hence, safer and effective biological therapy manifests to be in strong demand.
Finally, Ms. Shi also offered suggestions for us to protect the engineered bacteria in order to make the bacteria specifically release only in the proper intestinal environment. Acrylic resin should be used as the enteric coating. Based on different of pH, diverse materials can be chosen. In addition, although many researchers support the view that probiotics can shorten the duration of acute diarrhea illness, more experiments are needed to provide a definitive answer to the question on whether the engineered Lactococcus lactis can really regulate the micro-ecological balance in the intestine.
Activity: The Conference of China iGEMer Committee(CCiC)
From 26th to 28th August, organized by the iGEM team FAFU-CHINA, The Conference of China iGEMer Committee(CCiC) was held in Fujian Agriculture and Forestry University. Eighty three iGEM teams across the country with professors from School of Life sciences and doctors working on synthetic biology, 300 people totally, participated in this conference. The CCiC has been held for three consecutive times, and this year, the fourth was the largest communication platform for all iGEM teams in China. The conference lasted for 3 days, and simulated the agenda of the Giant Jamboree in Boston. The CCiC consisted of the presentation section and poster section. In addition, this year the CCiC conference had several special seminars in the evening of each meeting days. These seminars were delivered by from some of the current iGEMers. The presenters introduced the knowledge and concpts related to their projects and want to inspire other teams in the future. For example, in the seminar of the first night, the topics included microRNA and optogenetics. The concepts from these presenters introduced us to a totally new field how cell can be controlled by light.
In the CCiC, we had a presentation to share our ideas and thoughts with other teams. The presentation topics included how Staphylococcus aureus can affect human health, what probiotic strain is used as the host to run our circuit, the ideas in the design of the circuit and the problems we faced at that time. We hoped to get some advices from other teams to improves our work. Fortunately, TMMU has shared a similar project with us, thus we had same common problem in our work. A professor from TMMU came up a question on how our antimicrobial peptides can specifically target on S.aureus and without affecting other probiotic in the guts. A common problem on the circuit construction for our two teams was how to deal with cloning the agrC and agrA genes. Both of us found that the agrA gene had a very high tendency to be mutated during cloning. During our conversation, we suspected that protein AgrA might be a toxic protein for Lactococcus Lactis, thus it cannot be inherited stably. We improve our project based on the comments from other iGEM teams and iGEM the HQ judge’s suggestions during the conference.
In this conference, many interesting projects attracted us a lot. We studied from some ingenious designs on how to construct a much more complex pathway. Circuit design in synthetic biology is requires understanding of knowledge from many different fields and very precise design in assembly of many different parts with various functions. We keeps learning and acquiring more knowledge on gene expression and metabolic coordination of cells to improve our premature project in the future.
Activity: Visit to Shanghai Changhai Hospital
In order to get broader knowledge and feedback, we managed to book a consultation with Shanghai Changhai Hospital, an upper first-class general hospital in Shanghai, China. We invited Prof. Can Xu, who is specialized in Gastroenterology, especially the diagnosis and treatment of the inflammatory bowel disease (IBD), which is closely related to our research. We intended to get a further understanding of the potential relationship between IBD and Methicillin-Resistant Staphylococcus aureus colonization (as described by many scientific papers and reports), however, which is to be honest unsurprisingly, this case is also rare in this hospital so they cannot provide information too detailed and advanced. However, we did learn from the talk; Prof. Xu, along with her colleagues, told us about how intestine actually functions as the biggest immune organ in human body, and how important is our intestinal flora system (which is a hot topic because of their close relationship with brain function and aging). After listening to our project details, they suggested us firstly, keep in mind that the intestinal flora system is sensitive and requires balance, so be careful to make any changes to it, i.e., try not to harm beneficial bacteria when you are trying to kill the pathogen. Secondly, they suggested that if we want this probiotic therapy to be widely applied, we need to ask for the permission of China Food and Drug Administration （CFDA）, as it’s introducing a genetically engineered organism to human body, which has the potential to harm our health in some way. In terms of our designed drug delivery method, they confirmed with us that the enteric coated tablets do work, and the application of this method does have a bright future. However, we may consult with a pharmaceutical company or factory to make everything work.
After the consultation, they took us to the inpatient department and allowed us to visit the patients suffering for gastrointestinal problems. The wards were fully occupied, which suggested the amount of people having related diseases are really not low. “To be responsible for providing a better life for everyone”, that’s what each one of us was thinking about at that time, and will always keep that in mind.
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