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Promising research for a new antibiotic

Photo: NIH/NIAID https://flic.kr/p/bpzxT4

A recent study in Nature identifying a potential new antibiotic garnered a lot of attention in the media and research community. Besides identifying a new antibiotic, the study used a method that has the potential to unlock significantly more antibiotics.

To learn more, Health Talk spoke with Courtney Aldrich, Ph.D., associate professor of medicinal chemistry in the College of Pharmacy and editor-in-chief of ACS Infectious Diseases, the first chemical-based journal on infectious diseases.

HealthTalk: Describe the problem of resistance to antibiotics?
Courtney Aldrich: Antibiotics revolutionized modern medicine and ended an era where infectious diseases were the leading cause of death. But by their very nature, microbes that cause disease can quickly adapt and become resistant to antibiotics. All microorganisms can evolve and mutate to develop resistance. Additionally, once they acquire resistance, it can be transferred between organisms. We call that horizontal transfer. The result is that organisms that cause disease become more and more resistant to the drugs we use.

After a golden age of antibiotic discovery, roughly the 1940s through the 1960s, we have essentially not been able to develop new antibiotics fast enough to stay ahead of drug resistance.  Part of this is economics. It is not economically viable to research and develop a drug that will become ineffective over time.  So by the 1990s, most pharmaceutical companies had cut their antibiotic research programs.

For many infections, there is at least one antibiotic that is effective. But we are reaching a point where we may no longer have antibiotics to treat certain infections.

HT: What was most significant about the study?
Aldrich: First, there is the discovery of a new antibiotic, teixobactin, which appears to be effective and have a low propensity for developing resistance.The other innovation is the method used to isolate and culture bacteria.

Virtually all antibiotics are isolated from soil microorganisms. But most estimates say we can only culture about 1 percent of the microorganisms from the soil. The rest have not been conducive to growing when taken out of their natural environment.

What the researchers did in this case is develop what they call the iChip: a small device that allows cultivation of bacteria directly in their source environments. In this case, they used the iChip to take a single colony of bacteria, overlay a semi-permeable membrane and cover it with the same soil where the sample came from. This allowed the bacteria to grow in as close to its original environment as possible. If this method allows us to culture the other 99 percent of microbes from soil, or even a portion of that, there could be a vast reservoir for promising new compounds.

HT: Why does it seem this new drug will not develop resistance as quickly as other antibiotics?
Aldrich: The drug targets the bacterial cell-wall, not a protein.  Proteins can develop resistance spontaneously through mutation of their respective gene. But if a drug binds to the cell-wall, the structure of the cell-wall would have to change and that is not easily done in a single-step mutation. We have known targeting the cell-wall is very effective, so it is conceivable this new drug could be a useful antibiotic for decades before resistance develops.

How long will it take to continue study of this potential new antibiotic before it might be available for use by humans?
Aldrich: It can take several years. I think the researchers will do larger animal model testing and more detailed toxicology studies. From the data they presented, it appears the drug has favorable pharmacokinetics and is long-lived in the serum. Most likely chemistry efforts will be required to modify the molecule to improve its activity and drug disposition properties.

Another factor is producing the compound. The ability to produce large amounts of the teixobactin is unknown at the moment. It can take many years to  develop an optimized fermentation method and isolation procedure to produce large amounts of a new antibiotic.

Finally, one drawback is that the drug cannot be taken in pill-form. It will need to be injected. So if after continued study it remains a promising, effective new antibiotic, it will most likely be used in health care facilities like hospitals.

Read the full study in Nature.

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