Type IV pili promote early biofilm formation by Clostridium difficile

Authors

Grace A. Maldarelli, University of Maryland School of Medicine
Kurt H. Piepenbrink, University of Maryland School of MedicineFollow
Alison J. Scott, University of Maryland School of Dentistry
Jeffrey A. Freiberg, University of Maryland School of Medicine
Yang Song, University of Maryland School of Medicine
Yvonee Achermann, University of Maryland School of Dentistry
Robert K. Ernst, University of Maryland School of Dentistry
Mark E. Shirtliff, University of Maryland School of Dentistry
Eric J. Sundberg, University of Maryland School of Medicine
Michael S. Donnenberg, University of Maryland School of Medicine
Erik C. von Rosenvinge, University of Maryland School of Medicine

Date of this Version

6-30-2016

Document Type

Article

Citation

Pathog Dis. 2016 Aug 1; 74(6): ftw061. Published online 2016 Jun 30. doi: 10.1093/femspd/ftw061 PMCID: PMC5985507 PMID: 27369898

Abstract

Increasing morbidity and mortality from Clostridium difficile infection (CDI) present an enormous challenge to healthcare systems. Clostridium difficile express type IV pili (T4P), but their function remains unclear. Many chronic and recurrent bacterial infections result from biofilms, surface-associated bacterial communities embedded in an extracellular matrix. CDI may be biofilm mediated; T4P are important for biofilm formation in a number of organisms. We evaluate the role of T4P in C. difficile biofilm formation using RNA sequencing, mutagenesis and complementation of the gene encoding the major pilin pilA1, and microscopy. RNA sequencing demonstrates that, in comparison to other growth phenotypes, C. difficile growing in a biofilm has a distinct RNA expression profile, with significant differences in T4P gene expression. Microscopy of T4P-expressing and T4P-deficient strains suggests that T4P play an important role in early biofilm formation. A non-piliated pilA1 mutant forms an initial biofilm of significantly reduced mass and thickness in comparison to the wild type. Complementation of the pilA1 mutant strain leads to formation of a biofilm which resembles the wild-type biofilm. These findings suggest that T4P play an important role in early biofilm formation. Novel strategies for confronting biofilm infections are emerging; our data suggest that similar strategies should be investigated in CDI.