Abstract
Uropathogenic E. coli (UPEC), which cause urinary tract infections (UTI), utilize type 1 pili, a chaperone usher pathway (CUP) pilus, to cause UTI and colonize the gut. The pilus rod, comprised of repeating FimA subunits, provides a structural scaffold for displaying the tip adhesin, FimH. We solved the 4.2 Å resolution structure of the type 1 pilus rod using cryo-electron microscopy. Residues forming the interactive surfaces that determine the mechanical properties of the rod were maintained by selection based on a global alignment of fimA sequences. We identified mutations that did not alter pilus production in vitro but reduced the force required to unwind the rod. UPEC expressing these mutant pili were significantly attenuated in bladder infection and intestinal colonization in mice. This study elucidates an unappreciated functional role for the molecular spring-like property of type 1 pilus rods in host-pathogen interactions and carries important implications for other pilus-mediated diseases.
Highlights
To mediate colonization of host and/or environmental habitats, Gram-negative bacteria encode a highly conserved family of adhesive pili called chaperone-usher pathway (CUP) pili
The best-studied CUP pili are those encoded by uropathogenic E. coli (UPEC), which is the causative agent of the majority of urinary tract infections (UTIs)
Taken together our results show that the identity of residues within the FimA rod, are critical for the type 1 pili mediated virulence of UPEC in the urinary tract and suggest that the helical pilus rod has an important functional role, beyond serving as a platform to present fibrillum made up of the adhesin protein (FimH), in promoting colonization in the gut and infection of the bladder
Summary
To mediate colonization of host and/or environmental habitats, Gram-negative bacteria encode a highly conserved family of adhesive pili called chaperone-usher pathway (CUP) pili. CUP pili are critical virulence factors in a wide range of pathogenic bacteria, including Escherichia, Klebsiella, Pseudomonas, Haemophilus, Salmonella and Yersiniae genera (Nuccio and Baumler, 2007). 38 distinct CUP pilus types have been identified in Escherichia and Shigella genomes and plasmids, each of which is hypothesized to promote bacterial colonization of a distinct habitat (Nuccio and Baumler, 2007; Wurpel et al, 2013). The best-studied CUP pili are those encoded by uropathogenic E. coli (UPEC), which is the causative agent of the majority of urinary tract infections (UTIs). UTI treatment failure is common, with ~25% of woman suffering from recurrent UTI
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