Research

Pilus biogenesis

Bacterial pili are hair-like surface-exposed organelles. They are responsible for recognition of and attachment to the host and thus, are also crucial virulence factors. Pili are polymer of protein subunits, the assembly of which require accessory proteins. There are two biogenesis pathways for the production of pili in Gram-negative bacteria: the chaperone- usher pathway and the type IV pilus biogenesis pathway - not to be confused with T4S systems! We are engaged in research on both, but have made most progress on the former. Chaperone-usher (CU) pili have clear relevance in the pathogenicity of uropathogenic Escherichia coli, where CU pili mediate bacterial tropism to the bladder to cause cystitis or to the kidney to cause pyolenephritis. CU pili require two accessory proteins for biogenesis: a chaperone that stabilises pilus subunits and ferries them to an assembly platform, the usher, the second accessory protein required in this system. The usher is an extraordinary molecular nanomachine embedded in the outer membrane. It drives subunit recruitment, polymerisation and secretion. All in one protein!

References

Please click on the links below to download recent reviews and also our landmark papers in Nature, Science, and Cell. Hospenthal MK, Redzej A, Dodson K, Ukleja M, Frenz B, Rodrigues C, Hultgren SJ, DiMaio F, Egelman EH, Waksman G (2016) Structure of a Chaperone-Usher Pilus Reveals the Molecular Basis of Rod Uncoiling. Cell 164, 269–278 Waksman G (2017) Structural and molecular biology of a protein-polymerising nanomachine for pilus biogenesis. J. Mol. Biol. 429:2654- 2666. John Kendrew’s 100th anniversary special edition. Geibel S, Procko E, Hultgren SJ, Baker D, Waksman G (2013) Structural and energetic basis of folded-protein transport by the FimD usher. Nature. Apr 11;496(7444):243-6. doi: 10.1038/nature12007. G. Phan, H. Remaut, T.Wang, W. Allen, K. Pirker, A. Lebedev, N. Henderson, S. Geibel, E. Volkan, J. Yan, M. Kunze, J. Pinkner, B. Ford, C. Kay, H. Li, S. Hultgren, D. Thanassi, and Waksman G (2011). Crystal structure of the FimD usher bound to its cognate FimC:FimH substrate. Nature. 474:49-53. K.W. Dodson, J.S. Pinkner, T. Rose, G. Magnusson, S.J. Hultgren, and Waksman G (2001). Structural Basis of Tropism of Pyelonephritic /E. coli/ for the Human Kidney. Cell. 105:733–743. F.G. Sauer, K. Fütterer, J.S. Pinkner, K.W. Dodson, S.J. Hultgren, and Waksman G (1999). Structural basis of chaperone function and pilus biogenesis. Science. 285:1058-1061. Copyleft notice: The text of this webpage is available for modification and reuse under the terms of the Creative Commons Attribution-Sharealike 3.0 Unported License and the GNU Free Documentation License.
Pui