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The ability of the opportunistic pathogenClostridioides difficile to cause disease is closely linked to its propensity to adapt to conditions created by dysbiosis of the human gut microbiota. The cobamide (vitamin B12 ) metabolism ofC. difficile has been underexplored, although it has seven metabolic pathways that are predicted to require cobamide-dependent enzymes. Here, we show thatC. difficile cobamide metabolism is versatile, as it can use a surprisingly wide variety of cobamides and has alternative functions that can bypass some of its cobamide requirements. Furthermore,C. difficile does not synthesize cobamidesde novo but produces them when given cobamide precursors. A better understanding ofC. difficile cobamide metabolism may lead to new strategies to treat and preventC. difficile -associated disease.

Flexible Cobamide Metabolism in Clostridioides ( Clostridium ) difficile 630 Δ erm