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 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. F.   G.   Sauer,   J.   Pinkner,   G.   Waksman ,   and   S.J.Hultgren   (2002)   Chaperone   Priming   of   Pilus   Subunit   Facilitates   a   Topological   Transition   that Drives Fiber Formation . Cell . 111:543-51. Waksman sole corresponding author 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.

Pui