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

Atul K. Johri ,^1,, Immaculada Margarit,^2, Mark Broenstrup,^3, Cecilia Brettoni,² Lei Hua,¹ Steven P. Gygi,³ John L. Telford,² Guido Grandi,² and Lawrence C. Paoletti^1*

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts,¹ Novartis Vaccines and Diagnostics, via Fiorentina 1, 53100 Siena, Italy,² Department of Cell Biology, Harvard Medical School, Boston, Massachusetts³

Received 20 April 2006/ Returned for modification 12 September 2006/ Accepted 21 December 2006

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 level 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 (t_d) of 1.8 h with oxygen invaded human ME-180 cervical epithelial cells in large numbers compared with those grown at the same t_d without oxygen or at a slower t_d of 11.0 h. The fact that several GBS type V cell wall-associated and membrane proteins were expressed exclusively under the invasive growth condition prompted an investigation, using genomics and proteomics, of all upregulated genes and proteins. 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.

Published ahead of print on 8 January 2007.

Editor: V. J. DiRita

These authors contributed equally to this research.

Present address: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

Present address: Sanofi Aventis, Building H811, 65926 Frankfurt am Main, Germany.