The number of drug-resistant tuberculosis (TB) cases is rising globally. But a newly discovered natural antibiotic – produced by bacteria from the lung infection in a cystic fibrosis patient – could help fight these infections. Lab testing reported in the Journal of the American Chemical Society shows that the compound is active against multi-drug resistant strains.
Starting with the famous first discovery of penicillin from mold, scientists have continued to search for natural sources of antibiotics. And as pathogens develop resistance to once-reliable medicines, the search has taken on a new urgency. By 2040, more than a third of all TB cases in Russia, for example, could show resistance to first-line drugs currently used to fight the disease, a recent report published in Lancet estimates. Among potential new drug sources are species of the bacterial genus Burkholderia that thrive in a wide range of habitats, from soil to the human lung. One way these microbes have adapted to these diverse environments is by making potent antibiotics to take out their competition. In light of the growing threat of drug-resistant bacteria, particularly among TB strains, Gregory L. Challis, Eshwar Mahenthiralingam and colleagues wanted to see if Burkholderia might produce a promising anti-TB compound.
The researchers discovered that one species, Burkholderia gladioli, which was isolated from the sputum of a child with cystic fibrosis, produces an antibiotic called gladiolin. The compound belongs to the same structural class as etnangien, another antibiotic that has been investigated for its ability to jam bacterial cell machinery. But etnangien is highly unstable. The researchers found that gladiolin is much more stable than etnangien, and could therefore potentially be a better drug candidate. Lab testing also showed that gladiolin blocked the growth of four drug-resistant TB strains.
The authors acknowledge funding from the Biotechnology and Biological Sciences Research Council (U.K.), the Wales Life Sciences Bridging Fund and a Marie Sklodowska-Curie Actions Fellowship.
Article: Discovery and Biosynthesis of Gladiolin: A Burkholderia gladioli Antibiotic with Promising Activity against Mycobacterium tuberculosis, Eshwar Mahenthiralingam, and Gregory L. Challis et al., Journal of the American Chemical Society, doi: 10.1021/jacs.7b03382, published online 22 May 2017.