About this item:

164 Views | 160 Downloads

Author Notes:

shonna.mcbride@emory.edu

Conceptualization: Emily C. Woods, Shonna M. McBride.

Formal analysis: Emily C. Woods, Adrianne N. Edwards, Shonna M. McBride.

Funding acquisition: Shonna M. McBride.

Investigation: Emily C. Woods, Adrianne N. Edwards, Kevin O. Childress, Joshua B. Jones, Shonna M. McBride.

Methodology: Emily C. Woods, Adrianne N. Edwards, Shonna M. McBride.

Project administration: Shonna M. McBride.

Resources: Shonna M. McBride.

Supervision: Adrianne N. Edwards, Shonna M. McBride.

Validation: Shonna M. McBride.

Visualization: Emily C. Woods, Adrianne N. Edwards, Shonna M. McBride.

Writing – original draft: Emily C. Woods, Shonna M. McBride.

Writing – review & editing: Emily C. Woods, Adrianne N. Edwards, Shonna M. McBride.

The authors would like to thank the members of the McBride lab for useful feedback on this manuscript and Graeme Conn for advice on apparent Kd calculations.

In addition, the authors would like to thank Mike Billingsley, Gregory Tharp, Nirav Patel, and Steven Bosinger of the Yerkes Genomics Core Laboratory for assistance with the next-generation sequencing experiments and data analysis.

We thank David Smith and Yi Lasanajak of the Emory Comprehensive Glycomics Core for assistance with the SPR experiments and data analysis.

The authors are also grateful to Anice Lowen for the use of her ddPCR machine.

The authors have declared that no competing interests exist.

Subjects:

Research Funding:

This work was funded by grants DK087763 (National Institutes of Health Diabetes and Digestive and Kidney Diseases; https://www.niddk.nih.gov) to SMM, DK101870 (National Institutes of Health Diabetes and Digestive and Kidney Diseases; https://www.niddk.nih.gov) to SMM, AI109526 (National Institutes of Health Allergy and Infectious Diseases; https://www.niaid.nih.gov) to SMM, AI121684 (National Institutes of Health Allergy and Infectious Diseases; https://www.niaid.nih.gov) to SMM, and GM008169 (National Institutes of Health General Medical Sciences; https://www.nigms.nih.gov) to ECW.

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • Parasitology
  • Virology
  • ANTIMICROBIAL PEPTIDE LL-37
  • TOXIN GENE-EXPRESSION
  • CLOSTRIDIUM-DIFFICILE
  • ESCHERICHIA-COLI
  • PSEUDOMEMBRANOUS COLITIS
  • DEPENDENT REGULATION
  • IMMUNE-RESPONSE
  • SIGMA FACTORS
  • METABOLISM
  • RESISTANCE

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

Journal Title:

PLoS Pathogens

Volume:

Volume 14, Number 8

Publisher:

, Pages e1007153-e1007153

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© 2018 Woods et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
Export to EndNote