Programmable Approach To Combat Antibiotic Resistance

Programmable RNA antibiotics are introduced in the form of short antisense oligonucleotides (ASOs) that are coupled to small peptides to carry them inside the bacteria.

Programmable Approach To Combat Antibiotic Resistance

Antibiotic resistance is one of the greatest threats of the current era. The golden age of antibiotics, initiated by the discovery of penicillin, is now coming to an end due to antibiotic resistance. Most of the bacteria are multi-drug resistant, and some are even extensive drug-resistant XDR.

Antibiotic resistance refers to the ability of bacteria or other microorganisms to resist the effects of antibiotics, rendering them ineffective in treating bacterial infections.

In such a chaotic situation, scientists are always looking for novel drugs to combat these pathogens in a targeted and effective manner. Most currently available antibiotics are broad-spectrum, i.e., they are not able to deplete a single species from a pool of microbiota.

These antibiotics cannot target a single species of bacterium and sometimes also deplete favourable microbiota. Recent progress in bacterial RNA biology has provided a solution to this problem. mRNAs are explored to accelerate the development of programmable RNA antibiotics for microbiome editing and other applications.

mRNA-based programmable antibiotics:

During the period of COVID-19, scientists from all over the world worked diligently to make a vaccine against the Corona virus. Spikes of proteins, DNA, and RNA from viruses were targeted to make an effective vaccine.

Out of all vaccines, mRNA-based vaccines have impressively demonstrated their potential. These vaccines were highly effective and protected millions of people from getting diseases.

The wonders of RNA-based drugs are not just limited to viruses. They can also be used as candidates to develop programmable antibiotics to treat bacterial infections. Researchers from the University of Würzburg (JMU) and teams from the Institute of Molecular Infection Biology (IMIB) worked on bacterial strains of the type “uropathogenic Escherichia coli (UPEC)” to test the working of mrna-based antibiotics.

Antisense technology:

To create programmable antibiotics, anti-sense technology is exploited. The short chains of bases are introduced into bacteria that are designed to exactly match specific genes. When these fragments bind to the corresponding mRNA of the gene of interest, the production of proteins is retracted, and as a result, the bacterium dies.

Programmable RNA antibiotics are introduced in the form of short antisense oligonucleotides (ASOs) that are coupled to small peptides to carry them inside the bacteria.

These anti-sense oligonucleotides precisely examine bacterial communities, silence mRNAs of essential genes, and only eradicate targeted species, for example, antibiotic-resistant pathogens.

Novel tools are needed to facilitate targeted treatment of pathogens and prevent antibiotic-resistant microbes from impeding the successes of modern medicine.

Queries regarding mRNA-based antibiotics:

Although mRNA-based antibiotics seem promising, there are still many questions regarding their true species specificity, potential off-targeting, choice of peptides for delivery, bacterial resistance mechanisms, and host response. These questions were addressed by scientists at Wurburg, and they found satisfactory answers to them.

When RNA antibiotics are translocated to bacteria, bacteria show an undesirable stress response, primarily when these biomolecules cross the bacterial membrane. This is mainly due to the fact that antisense peptide nucleic acids are comparatively large in size, but the good news is that it is possible to make these “base pair snippets” smaller. This phenomenon is not possible with conventional antibiotics.

These researchers also addressed the specificity of the designed active agents, particularly antisense peptide nucleic acids that target mRNAs of essential bacterial genes.

The research showed that the applied base pairs only block the gene of interest, so mRNA antibiotics actually block only one specific bacterial gene. So the targeted gene silencing by programmable mRNA-based antibiotics gives hope for replenishing the golden age of antibiotics that is about to end!