Antibiotics are the ‘wonder drugs’ to combat microbes. For decades, multiple varieties of antibiotics have not only been used for therapeutic purposes but practised prophylactically across other industries such as agriculture and animal husbandry. Increased demand for antibiotics across many sectors has allowed for less expensive and off-label uses of drugs. On the contrary, the enormous and irresponsible use of antibiotics has contributed significantly to the advent of multi-drug-resistant strains. Bacterial systems are complex and adaptive. When faced with disturbances such as antibiotic treatments, they survive, recover and evolve. Bacterial evolution against antibiotics involves resistance (increase in minimum inhibitory concentration (MIC)), tolerance (reduces the effectiveness of drug action) and persistence (tolerance in subpopulations) which synergistically interact through epistatic mutations increasing the number of resistant mutants. In addition, epigenetic modifications and biofilm formation further increase bacterial resistance. Phage therapy which was thought to be the best solution is also failing due to CRISPR and other innate bacterial defences. Development of newer antibiotics is slow and unreliable as it depends mainly on modifying the existing antibiotics.
To combat this issue we follow the motto ‘Prevention is better than cure’ by degrading the antibiotics before they are released into the environment so that no more resistant pathogens are created using engineered antibiotic-resistant bacteria. As they say ‘keep your friends close and your enemies closer’.
The specific objectives to accomplish our goal of combating antimicrobial resistance are:-
- To clone antibiotic degrading enzymes present in naturally occurring strains in E.coli and optimise it to degrade a large quantity of antibiotic quickly.
- To prevent bacterial transformation, conjugation and transduction so that our antibiotic degrading genes are not transferred to other organisms.
- To generate a user modulated tightly regulated ‘kill-switch’ in our bacterial system such that our bacteria deteriorates itself and also its DNA, which would further prevent the uptake of these antibiotic degrading genes by other organisms and also further mutations are prevented in already resistant strains.
We plan to show a proof of concept through the degradation of sulphonamides but this can be extended to any antibiotic by simply changing the antibiotic degrading genes involved.
- Short Name: #CombatingAMR
- Created on: June 14, 2020