Broad spectrum antibiotics not only eradicate the target pathogen, but are known to have catastrophic effects on the beneficial bacteria, causing lasting damage to the gut microbiome. As a result, patients are more likely to suffer from reinfections as well as subsequent digestive distress.

In contrast, narrow spectrum antibiotics target one, or a small group, of pathogenic bacteria, sparing the gut microbiome as a whole.

In this study, scientists looked in detail at the action of one such antibiotic; fidaxomicin. This narrow spectrum antibiotic is used in the treatment of C. difficile infection. It inhibits RNA polymerase (RNAP), preventing the transcription of DNA to RNA. Using cryo-electron microscopy the researchers were able to study detailed 3D imagery of the drug molecule in its interaction with C. diff. to understand the exact mode of action of fidaxomicin. They discovered that the drug binds to one particular amino acid on RNAP; an amino acid that is lacking from the main groups of commensal bacteria.

The researchers propose that this new understanding may help in the development of other narrow spectrum antibiotics.

Xinyun Cao et al. (2022) Basis of narrow-spectrum activity of fidaxomicin on Clostridioides difficile. Nature.

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