The fall of Recalcitrance

This week, lets talk about the resistance in bacteria, or in unicellular parasitic prokaryotes in general. In a glance, resistance might suggest building immunity against that particular agent or host or mechanism.

But resistance is so much more than that. How does bacteria know that they have to mutate a particular protein in order to avoid the antibiotic from binding at that active site. How does bacteria know when to efflux the antibiotic out. How does theses smart cells know how to misguide the antibiotic with another mimicking target. Well, in a series of thought, one can think that bacteria earlier did not had these mechanisms. So what led these smart peeps to counter the antibiotics.

The answer requires scientific study and cannot be answered with a hypothesis alone. It is intriguing to think of bacteria’s as a collection of biomolecules working in a coordinated and systemic manner. Ever thought of how these non-living entities manage to build up one hell of a living being. How these smart asses work in a coordinated manner to bring about life into play. This is what i like the most about these creatures, how life arises from such non-living entities, and when you think and study about how these coordinations take place, you are in for a life time of roller coaster ride.

So, back to the point of resistance. For one thing that we are not fully aware of bacteria’s full genome capabilities and moreover, their gene sharing prowess by transduction, conjugation tubes and other mechanisms. These gene sharing capabilities is what makes them so tough and resistant, well, not always but sometimes the resistant genes are transferred from one organism to another. Our question here is, where does THAT cell gets its resistance from !

So, lets begin the hypothesis, Shall we !

Unicellular organisms are dynamic entities. The fact they have survived for over a million years tells a lot about them. They can easily adapt to changes in environmental conditions as compared to unicellular and multicelluar eukaryotes owing to the small size of the genome. The small size has the advantage of rapid mutations and replications without causing any significant repurcussions to itself. It also allows the bacteria to gain additional functionality unlike that of eukaryotes in which everything is so interliked that if you disturb a single base-pair of a gene in a pathway, the whole pathway malfunctions and disorders result, an example would be that of cystic fibrosis.

A hypothesis might be that when the antibiotic attacks the bacteria everytime after it’s in contact with the cell, over a couple of generations, the cell had to be deficient in that enzyme and not be dead at the least. So, when the enzyme is deficient the cell will find ways to complete that pathway or task. So, how does it do this. Consider, that the expression of the protein/enzyme and its concomitant antibiotic mediated suppression in the pathway will result in a stress on the translation and transcription of the target protein.

This stress induced in the cell might generate single nucleotide change in the DNA, thus altering its folding (Considering how fickle its configurations and conformations are relative to the DNA sequence) and………

So, after this alteration several things can happen,

1. No change in activity, Antibiotic is unable to bind to the enzyme thus making the cell resistant.
2. Change in activity of the cell resulting in infinite number of possibilities(which i am not ready to go into), Antibiotic still binds to the enzyme.
3. No change in activity, Antibiotic still binds to the enzyme.
4. Change in activity, Antibiotic doesn’t bind to the enzyme.

Now change in activity can mean either increase or decrease of the enzyme activity. But we can get a 50% chance of antibiotic resistance. Although all these four events aren’t equally likely and this likeness cannot be easily predicted.

But you get the idea, right !

Now, considering option 1, there is no change in activity, therefore, the cell is undergoing normal cycles. But in option 4, there can be two possibilities, either the activity will decrease or increase. The cell will then adjust the enzyme expression such that the expressed enzyme will give only the desired amounts of products. Anyways, these smart pants will be resistant !

Other than the mechanism proposed above(By me), some other possible mechanisms, as already stated can be horizontal gene transfers, random mutations etc.

Cells aren’t clever, they are just manipulated from the beginning in such a way that they don’t need a process control to keep they steady or alive, they can adapt themselves, a unique characteristic of living beings.

Now, how the manipulations aroused is a topic for another blog.

Thanks for sticking till the end. I hope you i get appreciated by the science community for this (Giggles).