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

• Published in: PLoS pathogens 2018-08, Vol.14 (8), p.e1007153-e1007153
• Main Authors: Woods, Emily C, Edwards, Adrianne N, Childress, Kevin O, Jones, Joshua B, McBride, Shonna M
• Format: Article
• Language: English
• Subjects: ABC transporter; ABC transporters; Adaptation; Adaptation, Physiological - genetics; Animals; Antibiotic-associated colitis; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Cationic Peptides - immunology; Antimicrobial peptides; Bioinformatics; Biology and Life Sciences; Cathelicidins; Cell surface; Clostridioides difficile - physiology; Clostridium Infections - genetics; Clostridium Infections - immunology; Cricetinae; Drug resistance; Female; Gene expression; Gene Expression Regulation, Bacterial - genetics; Gene regulation; Genes, Bacterial - genetics; Genetic aspects; Genomes; Host-Pathogen Interactions - physiology; Immune Evasion - genetics; Immunology; Infections; Intestine; Male; Medicine; Medicine and Health Sciences; Mesocricetus; Metabolism; Mice; Mice, Inbred C57BL; Operon - genetics; Pathogenesis; Peptides; Physical Sciences; Regulatory mechanisms (biology); Research and Analysis Methods; Risk factors; Transcription; Transcription (Genetics)
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1007153

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.