Antibiotics: Two Antibacterial Compounds Effective Against Resistant Tuberculosis Discovered

Researchers have just identified two compounds with antibacterial properties that could eventually lead to the development of antibiotics against tuberculosis.



Tuberculosis is a contagious lung disease caused by an infection with Mycobacterium tuberculosis and is sometimes considered a disease of the past. However, a recently published report of the World Health Organization (WHO) has shown that tuberculosis, with 1.5 million deaths in 2017, is now more deadly than HIV (770,000 deaths in 2018). In addition, an estimated 10 million people have contracted tuberculosis by 2018: 5.7 million adult men, 3.2 million adult women, and one million children.

Although there is now a tuberculosis vaccine (Bacille Calmette-Guérin (BCG)) and five major tuberculosis drugs (rifampicin, isoniazid, ethambutol, streptomycin, and pyrazinamide), the fight against the disease is far from over. In fact, currently, there are TB bacteria that may be resistant to one or more drugs, including the two most effective ones (isoniazid and rifampicin), or even to all the drugs available.

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The search for new antibiotics is therefore essential to combat this multi-resistance of the bacteria responsible for tuberculosis. Thanks to a discovery by researchers from the John Innes Centre in the United Kingdom, this could soon be the case. In a study published in the Journal of Antimicrobial Chemotherapy, they stated that they evaluated two compounds with antibacterial properties that make them serious candidates for antibiotics to combat tuberculosis.

Two compounds that do not cause bacterial resistance

As the research team explains in a press release, the strategy for the search for new treatments is to find compounds that exploit the targets of existing and known drugs. DNA Gyrase is a target for many antibiotics and a bacteria-specific protein that is essential for the replication of their circular chromosome.

These new compounds also attempt to inhibit their activity. Using X-ray crystallography, the research team has developed two compounds that target the DNA gyrase of TB bacteria. They discovered that surprisingly, a very common mutation in DNA Gyrase, which makes the bacteria resistant to a related group of antibiotics, the aminocoumarins, did not lead to resistance to the compounds under investigation here.

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“We hope that companies and academic groups working on the development of new antibiotics will find this study useful. It paves the way for further synthesis and investigation of the compounds that interact with this target,” said Professor Tony Maxwell, one of the lead authors of the paper.

“Resistance to antimicrobial agents is now widely recognized as one of the biggest problems we face in the 21st century. If we do not find solutions to this problem quickly, bacterial disease pandemics may occur in the future. People already know about the bubonic plague and other equally terrible diseases in history, but it is no exaggeration to say that these kinds of bacterial diseases could reappear if we do not have effective antibiotics. We need to find a way to bring together the knowledge of the academic and business worlds to act decisively,” he added.

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Structural and mechanistic analysis of ATPase inhibitors targeting mycobacterial DNA gyrase

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