The plasminogen binding protein PbsP is required for brain invasion by hypervirulent CC17 Group B streptococci

Germana Lentini, Angelina Midiri, Arnaud Firon, Roberta Galbo, Giuseppe Mancuso, Carmelo Biondo, Emanuela Mazzon, Annamaria Passantino, Letizia Romeo, Patrick Trieu-Cuot, Giuseppe Teti, Concetta Beninati

Research output: Contribution to journalArticle

Abstract

Streptococcus agalactiae (Group B Streptococcus or GBS) is a frequent cause of serious disease in newborns and adults. Epidemiological evidence indicates a strong association between GBS strains belonging to the hypervirulent CC17 clonal complex and the occurrence of meningitis in neonates. We investigate here the role of PbsP, a cell wall plasminogen binding protein, in colonization of the central nervous system by CC17 GBS. Deletion of pbsP selectively impaired the ability of the CC17 strain BM110 to colonize the mouse brain after intravenous challenge, despite its unchanged capacity to persist at high levels in the blood and to invade the kidneys. Moreover, immunization with a recombinant form of PbsP considerably reduced brain infection and lethality. In vitro, pbsP deletion markedly decreased plasmin-dependent transmigration of BM110 through brain microvascular endothelial cells. Although PbsP was modestly expressed in bacteria grown under standard laboratory conditions, pbsP expression was markedly upregulated during in vivo infection or upon contact with cultured brain endothelial cells. Collectively, our studies indicate that PbsP is a highly conserved Plg binding adhesin, which is functionally important for invasion of the central nervous system by the hypervirulent CC17 GBS. Moreover, this antigen is a promising candidate for inclusion in a universal GBS vaccine.

Original languageEnglish
Pages (from-to)14322
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Sep 25 2018

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    Lentini, G., Midiri, A., Firon, A., Galbo, R., Mancuso, G., Biondo, C., Mazzon, E., Passantino, A., Romeo, L., Trieu-Cuot, P., Teti, G., & Beninati, C. (2018). The plasminogen binding protein PbsP is required for brain invasion by hypervirulent CC17 Group B streptococci. Scientific Reports, 8(1), 14322. https://doi.org/10.1038/s41598-018-32774-8