Dirt Antibiotics: The Silver Bullets for Bacteria?

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Vancomycin

Vancomycin, the present generation of super-antibiotics, is one tenth less potent than Teixobactin when combating MRSA. Schematic created with Chem Draw 14. Copyright image by John A. Jaksich, all rights reserved.

Antibiotics in the twentieth century saved lives, reduced suffering, and then people started misusing them. Antibiotics, derived from bacteria, constitute molecular signatures from bacterial adaptations. These molecular secretions have become the promoters of infection. You can look at bacterial adaptations to antibiotics as accelerated evolutionary events – which, unfortunately, resulted in resistance and so-called ‘Superbugs.’

Interestingly, a newly discovered antibiotic, derived from a sample of common soil, may be the answer to today’s Superbugs.

Penicillin Was Discovered in 1928

Between 1930 and 1980, researchers discovered dozens of novel antibiotics by looking closely at bacteria and hunting for bacterial metabolites that disrupted competing bacteria. These metabolites became the present-day antibiotics.

In molecular terms, the drugs disrupted the mechanistic processes that allowed the bacterial infections to propagate through the body. Biologically speaking, drugs like penicillin attack bacteria by breaking into cellular structures and allowing the body’s white blood cells to finish the job.

However, since the 1980s, the discoveries of newer and better antibiotics slowed to a trickle when scientists used the initial paradigm of Alexander Fleming and medicinal chemists. Oftentimes the scientific paradigm (method of discovery) needs a revolution to correct itself, and this was the case with the search for new antibiotics.

In the 1990s, by utilizing the the genomes of bacteria, scientists set forward to attack  the molecular machinery in a more fundamental fashion. Through an understanding of how bacteria functioned in a deeper sense, scientists attempted to disrupt the bacterium from the inside-out.

Chemists, biologists, and the pharmaceutical community identified, in the individual bacteria, the genes responsible for inducing infections and tested millions of potential candidate molecules. Unfortunately, the results were less than impressive.

Peniclillin Molecule

Penicillin, discovered in 1928 by Alexander Fleming, heralded a new era for humanity in the twentieth century. However, although antibiotics improved many lives, there was a darker side.. Superbugs. Schematic with Chem Draw 14. Copyright image by John A. Jaksich, all rights reserved.

Mirror Image Molecules Aren’t What They Seem

On a molecular level the candidate molecules seemed to be a good antibiotic match. However, in practice, after more than eight years of research spent targeting at the genetic level-researchers only found five lead molecules.

With millions of research dollars spent, the results yielded a ‘bad research paradigm.’

While it may seem as though understanding the genomics surrounding bacterial infection would yield candidate molecules by beaker-ful-a more prominent bio-chemical concept comes into play.

Every individual may be considered as if he/she is a unique blueprint for fighting his/her own bacterial infections. Once a bacterium infects the body, it will mutate and adapt to the host (much like viruses or parasites).

Although much of the molecular machinery appears similar to the infecting agent- it is impossible to superimpose a mirror image upon itself. Tailoring molecules to fight an infection without knowing all of the details resulted in an incomplete molecular library of pharmaceuticals.

The millions of dollars already spent will most likely burn more research money to complete the project in the coming years (and possibly decades).

Teixobactin--new antibiotic

Researchers discovered the new antibiotic, Teixobactin, in an unprocessed sample of common soil. The antibiotic is reported to knock down 100 percent of all bacteria with no reported resistance. Schematic with Chem Draw 14. Copyright image by John A. Jaksich, all rights reserved.

A Possible Breakthrough in Antibiotic Research?

In the winter of 2015, a report of a new class of antibiotics emerged in the journal Nature. The international team of researchers found a type of new antibiotic that didn’t resemble any prior drug class. The lead molecule attacked bacteria in multiple ways (while previous classes of antibiotics disrupted one or two bacterial paths of infection). The mechanistic details outlined in the Nature article reveal a possible miracle drug.

The researchers, led by Dr. Kim Lewis of Northeastern University, report in their discovery that the novel molecule apparently had little to no mammalian toxicity. Amazingly the drug candidate knocked down the all of the worst bacteria presently known to humankind with no reported resistance.

The superbug, MRSA, is presently treated with a cocktail of antibiotics of which Vancomycin is the major drug. The super-antibiotic,  Teixobactin, reportedly uses one tenth of the Vancomycin cocktail.

 

How Does Teixobactin Work?

Teixobactin attacks at multiple sites-while 95 percent of all antibiotics attack the cellular walls containing the intact bacterium. More to the point, Teixobactin prevents the replication of the bacterium once infection has taken hold. As a result of the novel modes of action, it’s possible that the course of treatment could be shorter.

Antibiotics and Molecules: A Chemical Palette

The fortuitous discovery of Teixobactin presents to the researcher a large chemical palette from which to draw. The initial molecule is projected to be one of possibly many to come in the future.

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