NEW ANTIBIOTIC FROM A FORGOTTEN PROTOTYPE
Due to the rapid development of antimicrobial resistance, demand for the treatment of infections has increased significantly. Streptothricin, an antibiotic discovered in the early 1940s, was initially promising due to its activity against gram-negative bacteria. However, it was dropped due to the delayed renal toxicity effect. It was later known that Nourseothricin was a natural product made by a soil fungus, which contains multiple forms of a complex molecule called streptothricin. The main components of nourseothricin include streptothricin F (S-F, 1 lysine) and streptothricin D (S-D, 3 lysines). Delayed renal toxicity at >10-fold higher doses of S-F compared with S-D. Streptothricin-F binds with 16SrRNA of the bacterial ribosome and impinges on the decoding site where t RNA binds to the codon of the m RNA. This interaction leads to translation infidelity (scrambled protein sequences) and the resulting death of the bacterial cell.
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The above image has the chemical structure of streptothricin F and streptothricin D. |
On observing under cyro-electron microscopy, S-F binds primarily to a subunit of the bacterial ribosome, resulting in the translation errors induced. The binding interaction is distinct from other known translation inhibitors and can be comparatively more efficient.
REFERENCE:
Morgan CE, Kang Y-S, Green AB, Smith KP, Dowgiallo MG, Miller BC, et al. Streptothricin F is a bactericidal antibiotic effective against highly drug-resistant gram-negative bacteria that interacts with the 30S subunit of the 70s ribosome. PLOS Biology. 2023;21(5). doi:10.1371/journal.pbio.3002091
Henderson R by E. Reviving a forgotten antibiotic: Old drug shows new promise against Superbugs [Internet]. 2023 [cited 2023 Oct 24]. Available from: https://www.news-medical.net/news/20230517/Reviving-a-forgotten-antibiotic-Old-drug-shows-new-promise-against-superbugs.aspx
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