Structural and Evolutionary Analyses Show Unique Stabilization Strategies in the Type IV Pili of Clostridium difficile

Authors

• Kurt H. Piepenbrink, University of Maryland School of MedicineFollow
• Grace A. Maldarelli, University of Maryland School of Medicine
• Claudia F. Martinez de la Pena, University of Calgary
• Tanis C. Dingle, University of Calgary
• George L. Mulvey, University of Calgary
• Amanda Lee, University of Calgary
• Erik von Rosenvinge, University of Maryland School of Medicine
• Glen D. Armstrong, University of Calgary
• Michael S. Donnenberg, University of Maryland School of Medicine
• Eric J. Sundberg, University of Maryland School of Medicine

Date of this Version

2-3-2016

Document Type

Article

Citation

Structure. 2015 February 3; 23(2): 385–396. doi:10.1016/j.str.2014.11.018.

Comments

CC BY-NC-ND

Abstract

Type IV pili are produced by many pathogenic Gram-negative bacteria and are important for processes as diverse as twitching motility, biofilm formation, cellular adhesion and horizontal gene transfer. However, many Gram-positive species, including C. difficile, also produce Type IV pili. Here, we identify the major subunit of the Type IV pili of C. difficile, PilA1, and describe multiple three-dimensional structures of PilA1, demonstrating the diversity found in three strains of C. difficile. We also model the incorporation of both PilA1 and a minor pilin, PilJ, into the pilus fiber. Although PilA1 contains no cysteine residues, and therefore cannot form the disulfide bonds found in all Gram-negative Type IV pilins, it adopts unique strategies to achieve a typical pilin fold. The structures of PilA1 and PilJ exhibit similarities with the Type IVb pilins from Gram-negative bacteria that suggest that the Type IV pili of C. difficile are involved in microcolony formation.