The Beginning of the Story: Antibiotic Resistance
In 1929, British bacteriologist Dr. Alexander Fleming first discovered penicillin and opened thereafter a new era of antibiotics. Over the 20th century, the first commercial antibiotics led to the decrease in deaths due to infectious diseases from 50% to 10%. However, at the end of the 20th century and the beginning of the 21st, the rapid emergence of microbial antibiotic resistance becomes a global issue on public health care.
Antibiotic resistance is defined as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread.
Why Focus on Antibiotic Resistance: The Agricultural and Medical Background
In the 21st century, the resistant bacteria have a period of prosperity, which caused great losses worldwide:
There is a close relationship between agriculture and antibiotic resistance, because antibiotic resistance is easy to spread in livestock, intensive poultry farming and aquaculture as illustrated in figure 1. In 2017, some news reported vegetables and mussels contaminated with Gram-negative carriers of ESBL or KPC-3 carbapenemase in retail markets in North Africa, and imported seafood and raw dog food with the presence of MCR-1 positive E. coli isolates in Norway1, which highlighted the serious situations in agricultural field. Worse still, the leaked antibiotics can further pollute water and soil through food chains and other potential exposure, posing great threats to surrounding people and animals.
Figure 1. Geographical distribution of mcr-carrying bacteria2
Antibiotic resistance also brings immense impacts on medical fields. Firstly, it can threaten our ability to treat common infectious diseases, resulting in prolonged illness, disability, and even death. According to WHO statistics, 480,000 people suffer from multi-drug resistant tuberculosis (MDR-TB) every year globally. At least 10 countries, including Britain, France, Sweden, Australia and Japan, have demonstrated failure in the treatment of gonorrhea by the last-generation cephalosporins3. Secondly, without efficient antimicrobial medicines, risks of some significant medical procedures would rise drastically, such as organ transplantation, cancer chemotherapy, diabetes management and major surgery (for example, caesarean sections). Additionally, antibiotic resistance increases the costs of health care due to longer hospitalization duration and more demands on intensive care, putting extra burdens on low-income areas4.
Figure 2. Number of MDR-TB patients every year globally
In these cases, we see urgent needs of improvement in the detection of antibiotic resistance. Therefore, we are determined to facilitate the development of better detection, boosting the fight against antibiotic resistance.
The Challenges We Face
Antibiotic Abuse Surveillance
The emergence of drug-resistant microbes could be traced back fundamentally to the overuse of antibiotics. Take China as an example: 41%-60% of prescriptions in China include, which is above the WHO-recommended threshold of 30%. Moreover, the annual usage of antibiotics per capita reached 138g in China, which was 10 times more than that in the United States3. Artificial high-antibiotic-concentration environment will screen out bacteria with antibiotic resistance, which is referred to as "survival of the fittest". In light of this, it is urgent to control the abuse of antibiotics abuse at the very beginning.
Figure 3. The percentage of prescriptions including antibiotics in China
Figure 4. The annual use of antibiotics per capita
Difficulties in Diagnosis
Currently, some testing methods have been put into use to determine the specific resistant genes, such as mass spectrometer and real-time PCR. But there will be inevitable problems of expenses as not all hospitals can own this kind of expensive machines. The developed regions possess more medical resources, while the less-developed regions have barely no access to such costly testing devices, thus resulting in the inequality problems between different areas. In addition, the process of culturing samples gathered from patients with different medicines will take at least 6 hours, wasting precious time to treat patients.
What do We Want to Achieve?
The Detection of Antibiotics
The overuse of antibiotics over the years has in fact allowed for resistant bacteria to thrive. Spreading awareness and proper information in the society about the risks and consequences of the rapidly developing antibiotic resistance is essential in tackling this global problem. Therefore, we want to design a portable and convenient device that detects antibiotic molecules, which allowed everyone to get more acquainted with the potential antibiotic threats around us.
The Detection of Antibiotic Resistance Genes
The responses of the bacteria to overused antibiotics can result in mutational adaptations, acquisition of genetic material, or alteration of gene expression, which are the main causes of antibiotic resistance. Considering the unequal diagnostic ability in the society, we are inspired to design an affordable and accurate testing device. As for our targets, we chose two resistant genes MCR-1 and NDM because of their high prevalence in agriculture and resistance to current therapeutic agents.
To summarize, our project mainly focuses on two global issues: the overuse of antibiotics and the lopsided ability to detect antibiotic resistant genes. About the former issue, we take Kanamycin as an example and design an aptamer-based detector to provide the public a portable and convenient method of antibiotic molecules detection. we take MCR-1 and NDM as examples to verify the efficiency of our testing device.
1 Pieri A, Aschbacher R, Fasani G, et al. Country Income Is Only One of the Tiles: The Global Journey of Antimicrobial Resistance among Humans, Animals, and Environment. Antibiotics (Basel). 2020;9(8):473. Published 2020 Aug 1. doi:10.3390/antibiotics9080473
2 Nang SC, Li J, Velkov T. The rise and spread of mcr plasmid-mediated polymyxin resistance. Crit Rev Microbiol. 2019;45(2):131-161. doi:10.1080/1040841X.2018.1492902
3 Song Y, Han Z, Song K, Zhen T. Antibiotic Consumption Trends in China: Evidence From Six-Year Surveillance Sales Records in Shandong Province. Front Pharmacol. 2020;11:491. Published 2020 Apr 17. doi:10.3389/fphar.2020.00491