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Gut Pathogens
Published in: Gut Pathogens 1/2022

Open Access 01-12-2022 | Rifaximin | Short report

Myxopyronin B inhibits growth of a Fidaxomicin-resistant Clostridioides difficile isolate and interferes with toxin synthesis

Authors: Madita Brauer, Jennifer Herrmann, Daniela Zühlke, Rolf Müller, Katharina Riedel, Susanne Sievers

Published in: Gut Pathogens | Issue 1/2022

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Abstract

The anaerobic, gastrointestinal pathogen Clostridioides difficile can cause severe forms of enterocolitis which is mainly mediated by the toxins it produces. The RNA polymerase inhibitor Fidaxomicin is the current gold standard for the therapy of C. difficile infections due to several beneficial features including its ability to suppress toxin synthesis in C. difficile. In contrast to the Rifamycins, Fidaxomicin binds to the RNA polymerase switch region, which is also the binding site for Myxopyronin B. Here, serial broth dilution assays were performed to test the susceptibility of C. difficile and other anaerobes to Myxopyronin B, proving that the natural product is considerably active against C. difficile and that there is no cross-resistance between Fidaxomicin and Myxopyronin B in a Fidaxomicin-resistant C. difficile strain. Moreover, mass spectrometry analysis indicated that Myxopyronin B is able to suppress early phase toxin synthesis in C. difficile to the same degree as Fidaxomicin. Conclusively, Myxopyronin B is proposed as a new lead structure for the design of novel antibiotics for the therapy of C. difficile infections.
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Metadata
Title
Myxopyronin B inhibits growth of a Fidaxomicin-resistant Clostridioides difficile isolate and interferes with toxin synthesis
Authors
Madita Brauer
Jennifer Herrmann
Daniela Zühlke
Rolf Müller
Katharina Riedel
Susanne Sievers
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Gut Pathogens / Issue 1/2022
Electronic ISSN: 1757-4749
DOI
https://doi.org/10.1186/s13099-021-00475-9

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