Shuffling their Genetics

Antibiotic resistance happens when the germs no longer respond to the antibiotics designed to kill them. That means the germs are not killed and keep growing. This does not imply the fact that our body is resistant to antibiotics. It is lethal. Antibiotic resistance is a growing threat for humans. Other than increasing the risks of a minor surgery, it is making it difficult to treat life-threatening infections and diseases, such as tuberculosis, MRSA, and Gonorrhoea, etc.

One thing the researchers need to understand is that if they want to solve the antibiotic resistance mystery, they must know how to stop bacterial resistance. According to Dr. Celia Souque, a postdoctoral researcher at the University of Oxford, bacteria can cunningly reorganize their genetics to avoid the effects of an antibiotic. The bacteria have numerous ways of developing resistance. For instance, they can mutate to prevent antibiotics from targeting them and this can be done by altering the proteins inside the cell where antibiotics act. Also, bacteria attain genes that help them destroy molecules known as enzymes.

The above-mentioned tactics bring a cost for antibiotic resistant bacteria. A lot of energy is required to produce resistance enzymes, while modified proteins cannot work effectively as before. These factors harshly hinder bacteria and enable them to replicate a little slower than antibiotics that are not present, so resistant bacteria lose the competition against other bacteria for valuable resources and nutrients, which threaten their existence. Thus, resistant bacteria find a way to resist antibiotics while limiting the costs associated with it.

A recent study shows that a mechanism known as integron provides bacteria an incredible potential to gain an extraordinary level of resistance while reducing cost. This mechanism is little easier for antibiotic-resistant bacteria to live on and flourish.

Integrins Function
Integrins play a very important role during the transfer of virulence factor genes from one bacterium to another bacteria all through the horizontal gene transfer. This virulence transfer is largely mediated by integrins, which are bacterial genetic elements and are able to promote the acquisition and expression of gene embedded within the gene cassettes. The gene cassettes are some stretch of genes without having any promoter element at the very beginning normally.

Integrons are like bits of DNA and are exceptional to bacteria. Integrons allow bacteria to supply genes they attain from other resistant bacteria; these resistance genes are parallel in the genome of bacteria one after the other forming arrays and the position of genes in the arrangement has a great effect on the bacterial resistance level. The genes that are present toward the start of arrangement are highly expressed and offer high levels of resistance, while the gene at the back reduces the impact on the bacteria and retains silence and can be preserved at low cost.

Researchers find that integrase is an enzyme that provides the ability to re-arrange or shuffle the sequence of their genes, allowing bacteria to attune their resistance levels when need arises. When bacteria are at risk, integrase enzyme allows bacteria to cut off and move genes in the array. These integrons are beneficial for bacteria, therefore, researchers make custom integrons in the laboratory, holding relevant resistance genes in the very last position.

Experimental Evolution
In a study, the researchers defied bacteria with increasing doses of antibiotics. During the study, they observed the bacteria survival time. The method they used is called experiment evolution, which directly allows to measure how good bacteria are at evolving resistance. They found that bacteria can evolve resistance frequently and can shuffle their genes. Interestingly, this rearranging or shuffling is sometimes allied with the loss of other resistance genes that are present in bacteria. Against the selected antibiotic, bacteria lose some resistance genes in the process and once again become susceptible to other antibiotics by shuffling genes around. This shows that in bacteria, integrons have a role in evolving high levels of antibiotic resistance.

New Tactics
The results from the afore-mentioned study provide potential strategies to counteract integrons and contain their role in evolving resistance. For instance, antibiotics can interact with drugs that can inhibit the enzyme integrase to decrease gene re-ordering. Drugs that stop the bacteria’s “SOS response” the bacteria’s last resort reaction to antibiotics would also bound integron shuffling. This is called “anti-evolution” drugs, which have a role in preventing the evolution of resistance but they do not de-activate bacteria directly. Another alternative would be to expedite the integron shuffling to promote the loss of resistance genes by cycling through different antibiotics. This would direct the evolution of bacteria in a way that makes them sensitive to previously unusable antibiotics.

However, antibiotics save uncountable lives every year and should be used to avoid further spreading of diseases and antibiotic-resistant bacteria. In sum, a better understanding of how bacteria evolve resistance will allow us to improve current antibiotics usage, as well as the ones to be developed in the future.