Team:IIT Madras/Background
What are antibiotics?
Antibiotics, also known as antimicrobial agents are drugs that fight infections caused by bacteria. The key word in the previous sentence is bacteria. Antibiotics will have no effect if taken during a a viral infection like common cold, most sore throats and the flu. However, bacterial infections are a threat too, and antibiotics have served us well in fighting them for over 70 years. So how do they work? Antibiotics are chemicals that interact adversely with different components of a bacterium's structure and/or metabolism, thus bringing about their demise. For example some antibiotics like penicillins attack the cell wall and rupture it, others like tetracyclines target protein synthesis. The diagram below shows some of the molecular targets of antibiotics on bacterial cells.
How does resistance develop?
The emergence of antimicrobial resistance is an evolutionary mechanism. The bacterial population consists of several variants for each of it's gene. Essential proteins are being targeted by most of the antibiotics, which is mostly docking of drug to the protein. Among the variants, few proteins could have a property like they can function but the drug can not dock to the protein anymore. Now, the bacterial cells which have these proteins become resistant.
Antimicrobial peptides
Antimicrobial peptides (AMPs) function differently from the antibiotic molecules as they do not inhibit any protein of the pathogenic bacteria. There are various type of AMPs. In most of the cases, AMP molecules bind to the cell-wall of the bacteria and pierce through the cell wall and break it.
Evolved Resistance Mechanism against anitmicrobial peptide
It has recently been shown that in vitro exposure of bacteria to slowly increasing cationic AMP concentrations over several hundred generations can result in reversible physiological adaptation and/or spontaneous, inheritable resistance to the peptide used. The most observed and hypothesized resistance mechanisms include :
- Alteration of bacterial cell surface charge density and pattern.
- Release of proteases, which break the peptide bonds in the anitimicrobial peptide.
- Trapping or extrusion of antimicrobial peptides.
- Biofilm formation could diminish the activity of antimicrobial peptides.
How would our system help in tackling the emergence of Antibiotic resistance?
As we all are familiar with the theory of natural selection, which says that the species which have adapted it's environment at best would be survive and selected for further generations. Bacteria is a species which has practically lived for billion years. On the course of time, bacteria has evolved to a level which is best for it's survival because of natural selection. The theory of natural selection also talk about trade-off between genes and their function, which is that if you mutate a gene (which gives a functional protein) you might get additional properties from the protein but you would also loose it's inherited property.
Based on the above theory, if we have designed our project to leverage the power of natural selection to eliminate antibiotic resistance. Our idea is being explained following :
We design a system which senses the population of pathogens and secretes the antimicrobial peptide. When we put the pathogenic bacterium under the selection pressure of antimicrobial peptide, most of the pathogens would die and the remaining pathogens might develope a resistance mechanism and can live happily in that environment. These resistant pathogens might follow one or more above mentioned mechanism to acquire resistance against the antimicrobial peptide, but they would be lesser efficient in comparison to normal pathogenic cells in stress-free environment.e.g. if the pathogen cells have changed their cell surface charge density, they might become lesser efficient in the uptake of food, adhere to surfaces etc. compare to a normal pathogenic bacterial cell in stree-free environment. Or if the pathogen cells have evolved proteases, they will not have any advantage over normal pathogen in stress free environment, hence it will not be selected out. etc.
We take the advantage of this phenomenon and design our own system to tackle antibiotic resistance.
