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The RNA polymerase inhibitor Fidaxomicin is the current gold standard for the therapy of<jats:italic>C.\u00a0difficile<\/jats:italic>\u00a0infections due to several beneficial features including its ability to suppress toxin synthesis in<jats:italic>C.\u00a0difficile<\/jats:italic>. In contrast to the Rifamycins, Fidaxomicin binds to the RNA polymerase switch region, which is also the binding site for Myxopyronin\u00a0B. Here, serial broth dilution assays were performed to test the susceptibility of<jats:italic>C.\u00a0difficile<\/jats:italic>and other anaerobes to Myxopyronin\u00a0B, proving that the natural product is considerably active against<jats:italic>C.\u00a0difficile<\/jats:italic>and that there is no cross-resistance between Fidaxomicin and Myxopyronin\u00a0B in a Fidaxomicin-resistant<jats:italic>C.\u00a0difficile<\/jats:italic>strain. Moreover, mass spectrometry analysis indicated that Myxopyronin\u00a0B is able to suppress early phase toxin synthesis in<jats:italic>C.\u00a0difficile<\/jats:italic>to the same degree as Fidaxomicin. Conclusively, Myxopyronin\u00a0B is proposed as a new lead structure for the design of novel antibiotics for the therapy of<jats:italic>C.\u00a0difficile<\/jats:italic>infections.<\/jats:p>","DOI":"10.1186\/s13099-021-00475-9","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T16:02:38Z","timestamp":1641484958000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Myxopyronin\u00a0B inhibits growth of a Fidaxomicin-resistant Clostridioides\u00a0difficile isolate and interferes with toxin synthesis"],"prefix":"10.1186","volume":"14","author":[{"given":"Madita","family":"Brauer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Z\u00fchlke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Riedel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5457-2552","authenticated-orcid":false,"given":"Susanne","family":"Sievers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"issue":"1","key":"475_CR1","doi-asserted-by":"publisher","first-page":"e00045-15","DOI":"10.1128\/mSphere.00045-15","volume":"1","author":"CM Theriot","year":"2016","unstructured":"Theriot CM, Bowman AA, Young VB. 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