Antibiotic Alternatives

In our group’s blog posts up until now, we have been discussing different aspects of antibiotics from a chemical standpoint. Now we will cover alternatives to antibiotics. Alternatives to antibiotics are important because the overuse of antibiotics is driving us to a post antibiotic age where nearly all bacteria will be resistant to antibiotics, rendering them useless. Continuing to use antibiotics at this rate will only accelerate us faster towards a post antibiotics age. We must look into alternatives so we can avoid a crisis.

Antimicrobial Peptide Chains

In this article, the prospect of using antimicrobial peptide chains is explored. Researchers at the Fraunhofer Institute for Cell Therapy and Immunology have identified 20 of these amino acid chains that are lethal to microbial organisms. They were even successful in inhibiting the growth of methicillin resistant Staphylococcus aureus (MRSA). The polypeptides contain enough cationic amino acids to give them a net positive charge. This net positive charge attracts them to and helps them penetrate through the cell wall of bacteria. These peptides begin to work within minutes and at a concentration 10x less than traditional antibiotics. They do not affect plants and humans because we have cholesterol in our cell membranes. Not only does the cholesterol act as a stabilizing agent, but it lessens the effect of the electrostatic interactions that the peptide chains rely on to enter the cell.

Examples of common antimicrobial peptides.

Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs)

PPMOs are a specific type of peptide chain that has also shown promise as an alternative to traditional antibiotics. A PPMO is a peptide conjugated phosphorodiamidate morpholino oligomer. It is a peptide chain that has been engineered as an analog to a DNA or RNA chain of the target organism. As a result, it has the capability of silencing the expression of certain genes. PPMOs are much more effective than traditional antibiotics and they work in cases where the organisms have become resistant to traditional antibiotics. This is because their mechanism is completely different. Instead of interfering with cellular functions, these antibiotic alternatives strike by going directly for the DNA.

Acyldepsipeptides

While many common antibiotics attempt to interrupt cellular function – inhibit protein synthesis, cell wall synthesis, or even nucleic acid functions – in bacterial cells, research has been done on new techniques of attacking bacteria cells. Researchers at Brown University and Massachusetts Institute of Technology have discovered a way to make the already effective acyldepsipeptides (ADEPs) even more potent by making these ADEPs more rigid. By swapping out many amino acids in the naturally occurring ADEPs, experiments were performed to see which structure would be the most rigid and robust. To test this experiment, researchers placed these molecules in a deuterium solution, or a solution of hydrogen atoms with one extra neutron. The deuterium atoms replace the hydrogen atoms on the ADEP itself (click on this link for more information on the chemical reaction!). A rigid molecule is considered one that has strong intramolecular forces, and if the rate of the deuterium-hydrogen atom reaction was too slow, the intramolecular forces were considered strong, making the molecule rigid.

A regular acyldepsipeptide (pictured on the left) and the various concentrations of bacteria in solution. A modified acyldepsipeptide (pictured on the right) functionalized with two methyl groups make the molecule much more rigid.

Watch this video for more information on antibiotic resistance!!!

All of these alternatives are very promising and hold a lot of potential for future medications. The common abuse and overuse of antibiotics has taken us to an era in which bacteria are becoming more and more resistant to these antibiotics. These antibiotic alternatives can help us avoid a true bacteria crisis. If we don’t follow certain tips and tricks, common antibiotics will no longer work, and we will have to rely on alternatives similar to antimicrobial peptides, PPMOs, and ADEPs.

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