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.