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Infect. Immun. doi:10.1128/IAI.00638-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Transcriptional and Proteomic Profiles of Group B Streptococcus Type V Reveal Potential Adherence Proteins Associated with High-Level Invasion

Atul K. Johri, Immaculada Margarit, Mark Broenstrup, Cecilia Brettoni, Lei Hua, Steven P. Gygi, John Telford, Guido Grandi, and Lawrence C. Paoletti*

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Novartis Vaccines and Diagnostics, via Fiorentina 1, 53100, Siena, Italy, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, U.S.A.

* To whom correspondence should be addressed. Email: lpaoletti{at}channing.harvard.edu.


   Abstract

Group B Streptococcus (GBS) is an opportunistic organism that can harmlessly colonize the human gut, vagina, and rectum but can also cause pneumonia, sepsis, and meningitis in neonates born to colonized mothers. We have shown previously that growth rate and oxygen regulate the ability of GBS to invade eukaryotic cells in vitro. Herein we extend and expand on these observations to show that GBS type V, an emergent serotype, grown in a chemostat at a cell mass-doubling time (td) of 1.8 h with oxygen invaded human ME-180 cervical epithelial cells in high numbers compared with those grown at the same td without oxygen or at a slower td of 11.0 h. That several GBS type V cell wall-associated- and membrane proteins were expressed exclusively at the invasive growth condition prompted an investigation of all upregulated genes and proteins using genomics and proteomics. Several proteins with potential roles in adherence were identified, including an undefined surface antigen (SAG1350), a lipoprotein (SAG0971), penicillin-binding protein 2b (SAG0765), glyceraldehyde-3-phosphate dehydrogenase (SAG0823) and an iron-binding protein (SAG1007). Mouse antisera to these five proteins inhibited binding of GBS type V to ME-180 cells by ≥85%. Recombinant undefined surface antigen (SAG1350), lipoprotein (SAG0971), and penicillin-binding protein 2b (SAG0765) each bound to ME-180 cells in a dose-dependent fashion, confirming their ability to act as ligands. Collectively these data increase the number of potential GBS adherence factors and also suggest a role for these surface-associated proteins in initial pathogenic events.







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J. Bacteriol. J. Virol. Eukaryot. Cell
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Copyright © 2007 by the American Society for Microbiology. All rights reserved.