A natural substance secreted by soil bacteria has proven that it can be developed into a new drug to treat tuberculosis, according to a new study published in the EMBO Molecular Medicine. The Swiss scientists ’research team revealed how the natural antibiotic pyrithromycin produced by the cystic bacterium bacterium works against tuberculosis bacteria. This promising drug candidate has a positive inhibitory effect on many tuberculosis bacteria that have been treated with the first-line drug isoniazid.
Some characteristics possessed by bacteria and some substances produced have powerful defense capabilities to protect bacteria from surviving in the bacteria habitat. Therefore, screening the natural products produced by these bacterial organisms is a powerful method to discover new drugs against infectious diseases. The lead author of this study, Stewart Cole, of the Higher Federal Institute of Technology in Paris, said that using this method we have shown that The antibiotic pyrithromycin has a selective inhibitory effect on Mycobacterium tuberculosis which induces human tuberculosis. At the same time, it is also active against mycobacteria treated with first-line drugs such as isoniazid. Each year, tuberculosis causes up to 2 million deaths. The development of new effective drugs is an urgent need, because the prevalence of multi-drug resistant tuberculosis is increasing, the effectiveness of antibiotics is greatly reduced, and drugs used to treat tuberculosis such as isoniazid and rifampicin are often no longer effective.
The researchers discovered a protein, NADH-dependent enoylase (acyl carrier protein) reductase or INHA, which is the main target of antibiotics. By separating and studying the genome sequence of the pyrithromycin-resistant mutant in Mycobacterium tuberculosis, researchers have discovered that a single gene named inhA is the main regulator of M. tuberculosis's resistance to this natural antibiotic, and the inhA gene is produced The essential gene of InhA protein, which is the target of the known anti-tuberculosis drug isoniazid.
Facts have proved that pyrithromycin can bind to an active pocket of the InhA enzyme like isoniazid, but unlike isoniazid, the binding method is different, which allows pyrithromycin to specifically inhibit mycobacterial drug resistance The drug resistance mechanism produced by the strain. In summary, the study found that pyrithromycin inhibits InhA to kill Mycobacterium tuberculosis, even the isoniazid drug that is resistant to clinically isolated bacteria.
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