Rebecca Tang

The introduction of antibiotics like penicillin to treat bacterial diseases revolutionized medicine in the 1940s. Most antibiotics work by disrupting synthesis of components essential for bacterial growth and survival. By interfering with these processes, antibiotics stop the progression of bacterial infections.

Unfortunately, bacteria mutate quickly, becoming resistant to existing antibiotics through several different methods. Bacteria can evolve to decrease the level of antibiotics that enters the cell, chemically modify the antibiotic to reduce its potency, or simply circumvent the antibiotic by developing alternate pathways for synthesizing key molecules. When bacteria develop resistance against an antibiotic, that drug can no longer be used to treat resulting infections.

Recently, the increased prevalence of bacteria resistant to a wide range of antibiotics, including methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant Mycobacterium tuberculosis (MDR-TB), has brought attention to the urgent need for new antibiotics. These highly resistant forms of staph and TB are notoriously difficult to treat and have high mortality rates.

MDR-TB
Multi-drug-resistant tuberculosis

Antibiotic discovery is challenging because the cell walls that envelop and protect bacteria are difficult to penetrate. Most existing antibiotics were discovered by isolating compounds produced by soil bacteria to kill their competitors. Thus far, attempts to artificially synthesize these antibacterial compounds have failed. Because of this, antibiotics can only be made by culturing bacteria and manipulating them to increase antibiotic production. However, over 99% of bacterial species cannot be cultured in the lab, severely limiting antibiotic discovery. The 1960s saw the end of the first generation of antibiotic discoveries.

Despite these challenges, Dr. Losee Ling and her colleagues reported the discovery of a new antibiotic called teixobactin in a recently published article in Nature. To overcome the difficulties of culturing bacteria in the lab, the authors created a device that not only isolates bacteria from soil but also allows nutrients from their natural environments to reach the bacteria. Using this method, Ling and her colleagues were able to recover 50% of bacterial cells from soil, compared to only 1% using traditional isolation and culturing methods. As a result, they were able to grow bacteria that had previously been unable to survive in the lab.

The authors created a device that not only isolates bacteria from soil but also allows nutrients from their natural environments to reach the bacteria.

The new ability to culture these bacteria allowed the authors to search for antibiotic compounds that the previously “unculture-able” bacteria might be producing. They found one sample containing compounds that successfully inhibited the growth of S. aureus, the bacteria responsible for staph infections. The authors purified the active compound and found a new molecule, which they named teixobactin. After further analyses, they found that teixobactin disrupts synthesis of peptidoglycan, the major component of bacterial cell walls. Without peptidoglycan cell walls, bacteria lacking proper physical support will explode and die.

Overall, teixobactin shows promise as a new line of antibacterial defense. In particular, teixobactin is potent against several bacterial pathogens that have historically proven difficult to treat, such as Clostridium difficile, a common hospital-acquired infection, and Bacillus anthracis, which causes anthrax. Teixobactin was also more effective than vancomycin, the last line of treatment for drug-resistant infections like MRSA, in killing some S. aureus populations. Additionally, S. aureus and M. tuberculosis did not become resistant to teixobactin even when growing in conditions suitable for developing antibiotic resistance. Since teixobactin is not only effective at killing bacteria but also difficult for bacteria to evade, it shows promise for therapeutic use.

Since teixobactin is not only effective at killing bacteria but also difficult for bacteria to evade, it shows promise for therapeutic use.

Teixobactin must undergo further testing before humans can use it, but the work thus far has already transformed antibiotic drug discovery. By developing a new method to culture bacteria, Ling and her colleagues have made it possible to screen many more soil bacteria for antibiotics. Teixobactin is the first member of a new class of drugs that are effective against several bacterial diseases that are currently untreatable because of antibiotic resistance. There are likely other natural antibacterial compounds waiting to be discovered using these techniques.

References

Ling, Losee L. et al. “A New Antibiotic Kills Pathogens without Detectable Resistance.” Nature 517.7535 (2015): 455–459. NCBI PubMed. Web.

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