American researchers have just identified two compounds with antibacterial properties which could eventually result in the development of antibiotics against tuberculosis.
- Both compounds target the DNA gyrase of the bacterium responsible for tuberculosis, a protein essential for its replication.
- No resistance to both compounds was found, paving the way for the development of new antibiotics against tuberculosis.
Contagious lung disease due to infection with Koch’s bacillus (Mycobacterium tuberculosis), tuberculosis is sometimes considered a disease of the past. However, a recent report by the World Health Organization (WHO) showed that with 1.5 million deaths worldwide in 2017, tuberculosis is currently more deadly than HIV (770,000 deaths in 2018). In addition, in 2018, 10 million people would have contracted tuberculosis, i.e. 5.7 million adult men, 3.2 million adult women and one million children.
Although there is now a vaccine against tuberculosis, as well as five major anti-tuberculosis drugs (rifampicin, isoniazid, ethambutol, streptomycin, and pyrazinamide), the fight against the disease is far from over. Indeed, in France and in other countries, there are resistant tuberculosis bacteria, which can resist a single drug or several, including the two most effective (isoniazid and rifampicin), or even all existing drugs.
The search for new antibiotics is therefore essential to counter this multi-resistance of the bacteria responsible for tuberculosis. Thanks to a discovery by researchers at the John Innes Center in the UK, that may soon be the case. In a study published in the Journal of Antimicrobial Chemotherapythey explain that they have evaluated two compounds with antibacterial properties that make serious antibiotic candidates for the fight against tuberculosis.
Two compounds that do not cause bacterial resistance
As the research team explains in a statement, the strategy for finding new treatments is to find compounds that exploit existing well-known targets for drugs. Target of many antibiotics, DNA gyrase is a specific protein of bacteria, which is essential for the replication of their circular chromosome.
These new compounds also seek to inhibit its activity. Using X-ray crystallography, the research team developed two compounds that target the DNA gyrase of bacteria that cause tuberculosis. They discovered that, surprisingly, a very common DNA gyrase mutation that makes bacteria resistant to a related group of antibiotics, the aminocoumarins, did not induce resistance to the compounds examined here.
“We hope that companies and academic groups working to develop new antibiotics will find this study useful. It paves the way for synthesis and further study of compounds that interact with this target.”said Professor Tony Maxwell, one of the lead authors of the work.
“Antimicrobial resistance is now well recognized as one of the biggest issues facing us in the 21stand century. If we don’t quickly find solutions to this problem, we could see outbreaks of bacterial diseases in the future. People know about the bubonic plague and other such terrible plagues by studying history, but it is no exaggeration to say that bacterial diseases of this type could reappear if we do not have effective antibiotics. We need to find a way to bring together the expertise of academia and business for decisive action“, he added.
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