IISER-Tirupati's iGEM project, Coli Kaze

This year we have planned to tackle the issue of antimicrobial resistance, AMR. 

Antibiotics are one of the pollutants that has been ignored by the general public to a very large extent. These antibiotics can become extremely dangerous by turning pathogenic bacteria into superbugs that can cause diseases with seemingly no cure. To be specific, we aim to degrade excess antibiotics that are being released into the environment via waste generated through poultry farms. The World Health Organization has announced the Global Action Plan on antimicrobial resistance (GAP) is the world’s blueprint for tackling the emergence and spread of antimicrobial resistance (AMR).  A recently published study looked at hospitalized adult patients in Wuhan, China, that had been diagnosed with COVID-19. The researchers found that half of the patients who died also had a secondary bacterial infection. Similarly, almost all diseases have increased fatality rates due to AMR. Our system of interest is poultry excreta as it is the largest contributor to AMR in India. Our project has an added advantage of preventing adverse drug effects and allergic responses to antibiotics as our project can be fine-tuned to degrade any antibiotic to potentially prevent many diseases caused due to drug exposures.

Major research is going on in the development of newer antibiotics, but mainly involves the modification of existing drugs. Also, there have been policy changes that have been made to regulate the quantity of antibiotics released into the rivers and environment. Animal husbandry is one of the major occupations of people of India, which is one of the major producers of meat and milk products. Poultry and Dairy farms use antibiotics mainly sulphonamides as growth promoters without any consultations from veterinarians. This results in a lot of antibiotic waste that is leaked into the surrounding environment causing severe antibiotic pollution. Surveys have shown that several of the most efficient antibiotic resistance prevention options involve high costs, investments in technology and are not sustainable. Few methods used, include anaerobic digestion of livestock waste, which is of interest in the project. This method degrades sulfonamides and trimethoprim, but the process takes five weeks and is not cost-efficient. Bruteforce solutions like incineration can also be adopted but owing to deteriorating air quality and destruction of potential bio-fertilizers, this is not a very feasible method. One direct way of removing both antimicrobial-resistant bacteria and antimicrobial resistance genes is via solid separation such as sedimentation. However, subsequent biological treatment steps may result in a selective increase in Antibiotic-Resistant Bacteria (ARB).

Given all these problems with the current methods of treating antibiotic waste produced from various sources, our genetically engineered bacteria will be of immense help as it contains a double gene system that would degrade the antibiotic (sulphonamides) combined with anti-conjugation genes and a user modulated kill-switch for preventing any horizontal gene transfer thus addressing the issue of biosafety and the above problems. The advantages of our system over the others are:-

● The antibiotic degradation plants are not very easy to install and also, not feasible. But with our engineered bacteria, we will be able to set up a plant easily.

● We plan on degrading only one class of antibiotics (sulfonamides) but this can be scaled up to degrade any class of antibiotics by using a large number of antibiotic degrading genes all cloned into a single organism.

● Our system will be faster and efficient than all the technology currently used to tackle this as bacteria grow and metabolize very quickly.

The COVID 19 pandemic has affected the pace of advancement of our project, but in no way has it affected our determination. We are planning the experiments that can be done to prove our sub-goals and also sketching out the layouts of various biobricks that we are planning to make. We are also applying to various funding agencies to gather the much-needed funds for our project. Apart from this, the dry lab team is working hard to find and modify appropriate models to mathematically model the working of our engineered bacteria and find specific parameters for our system to theoretically predict the working of our system. We also plan to design a piece of hardware that will work as a prototype to exhibit how our bacteria would work.