Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells
Version of Record online: 4 MAR 2011
© 2011 Blackwell Publishing Ltd
Volume 13, Issue 6, pages 885–896, June 2011
How to Cite
Jennings, M. P., Jen, F. E.-C., Roddam, L. F., Apicella, M. A. and Edwards, J. L. (2011), Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells. Cellular Microbiology, 13: 885–896. doi: 10.1111/j.1462-5822.2011.01586.x
- Issue online: 16 MAY 2011
- Version of Record online: 4 MAR 2011
- Accepted manuscript online: 10 FEB 2011 03:10AM EST
- Received 25 August, 2010; revised 26 January, 2011; accepted 2 February, 2011.
Expression of type IV pili by Neisseria gonorrhoeae plays a critical role in mediating adherence to human epithelial cells. Gonococcal pilin is modified with an O-linked glycan, which may be present as a di- or monosaccharide because of phase variation of select pilin glycosylation genes. It is accepted that bacterial proteins may be glycosylated; less clear is how the protein glycan may mediate virulence. Using primary, human, cervical epithelial (i.e. pex) cells, we now provide evidence to indicate that the pilin glycan mediates productive cervical infection. In this regard, pilin glycan-deficient mutant gonococci exhibited an early hyper-adhesive phenotype but were attenuated in their ability to invade pex cells. Our data further indicate that the pilin glycan was required for gonococci to bind to the I-domain region of complement receptor 3, which is naturally expressed by pex cells. Comparative, quantitative, infection assays revealed that mutant gonococci lacking the pilin glycan did not bind to the I-domain when it is in a closed, low-affinity conformation and cannot induce an active conformation to complement receptor 3 during pex cell challenge. To our knowledge, these are the first data to directly demonstrate how a protein-associated bacterial glycan may contribute to pathogenesis.