The C. difficile clnRAB operon initiates adaptations to the host environment in response to LL-37.

To cause disease， Clostridioides (Clostridium) difficile must resist killing by innate immune effectors in the intestine， including the host antimicrobial peptide， cathelicidin (LL-37). The mechanisms that enable C. difficile to adapt to the intestine in the presence of antimicrobial peptides are unknown. Expression analyses revealed an operon， CD630_16170-CD630_16190 (clnRAB)， which is highly induced by LL-37 and is not expressed in response to other cell-surface active antimicrobials. This operon encodes a predicted transcriptional regulator (ClnR) and an ABC transporter system (ClnAB)， all of which are required for function. Analyses of a clnR mutant indicate that ClnR is a pleiotropic regulator that directly binds to LL-37 and controls expression of numerous genes， including many involved in metabolism， cellular transport， signaling， gene regulation， and pathogenesis. The data suggest that ClnRAB is a novel regulatory mechanism that senses LL-37 as a host signal and regulates gene expression to adapt to the host intestinal environment during infection.