Kevin England (@kevinengland.bsky.social)

A sulfur-containing nucleoside antibiotic from Photorhabdus | mBio Introducing novel antibiotics is essential to counter the spread of drug-resistant pathogens. Here, we report the discovery of 4′-thiothymidine (4′sT), a nucleoside antibiotic from the nematode symbiont Photorhabdus asymbiotica, identified through activation of a silent biosynthetic gene cluster. 4′sT features an unusual 4′-thiosugar moiety. We identified its biosynthetic gene cluster, including a radical SAM enzyme presumably involved in sulfur incorporation. 4′sT exhibits strain-selective activity that is governed by differences in thymidine metabolism rather than variations in the molecular target. These findings expand our knowledge of antibiotics with unusual selective activity. https://journals.asm.org/doi/10.1128/mbio.02164-25