Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells

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Title Neisseria gonorrhoeae pilin glycan contributes to CR3 activation during challenge of primary cervical epithelial cells
Author Jennings, Michael Paul; Jen, Freda En-Chi; Roddam, Louise F.; Apicella, Michael A.; Edwards, Jennifer L.
Journal Name Cellular Microbiology
Year Published 2011
Place of publication United Kingdom
Publisher Wiley-Blackwell Publishing Ltd.
Abstract 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.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1111/j.1462-5822.2011.01586.x
Volume 13
Issue Number 6
Page from 885
Page to 896
ISSN 1462-5822
Date Accessioned 2011-03-15
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Medical Microbiology
URI http://hdl.handle.net/10072/40606
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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