Bacterial pathogens have evolved a wide range of strategies to adhere to cells and subsequently invade host tissues (Kline et al., 2009; Nobbs et al., 2009). In particular, many microorganisms, including both pathogens and commensals, are able to bind host plasminogen (Plg) on their surface, where its activation can be controlled by host or bacterial factors (Lahteenmaki et al., 2001; Bergmann and Hammerschmidt, 2007; Fulde et al., 2013). The aim of the studies presented in this thesis was to identify novel virulence factors of Streptococcus agalactiae or GBS that might be involved in binding to host factors, particularly Plg. First, a novel protein (Gbs0428 or PbsP) was identified by proteomics analysis of the GBS exoproteome and found to display two SSURE domains (Bumbaca et al., 2004), homologous with those of the previously characterized Plasminogen and fibronectin binding protein B (PfbB, also called PavB) of Streptococcus pneumoniae (Papasergi et al., 2010). Next, the role of Gbs0428 in the contest of GBS pathogenesis was investigated. After showing that Gbs0428 is a cell-wall-anchored surface protein that binds Plg, it was found that this adhesin is expressed by isolates belonging to all of the main GBS lineages, including strains of the hypervirulent clonal complex 17 (CC17), which is responsible for a large number of neonatal GBS infections, particularly meningitis cases. In the context of the CC17 prototype BM110 strain, PbsP was found to be markedly upregulated in vivo. PbsP was also found to bind Plg largely through the interaction between lysine-binding sites in the kringle 4 domain of Plg with a novel protein domain that was named MK-rich region. Moreover, PbsP-mediated Plg binding conferred proteolytic activity to GBS surface, which ensured GBS transmigration across endothelial cells and colonization of the brain. All together these data indicate that PbsP has an important role in the pathogenesis of GBS infections and might represent a target in alternative strategies to control GBS infection.

Functional and molecular characterization of PbsP (Plasminogen binding surface Protein) of Streptococcus agalactiae

ROMEO, LETIZIA
2017-02-19

Abstract

Bacterial pathogens have evolved a wide range of strategies to adhere to cells and subsequently invade host tissues (Kline et al., 2009; Nobbs et al., 2009). In particular, many microorganisms, including both pathogens and commensals, are able to bind host plasminogen (Plg) on their surface, where its activation can be controlled by host or bacterial factors (Lahteenmaki et al., 2001; Bergmann and Hammerschmidt, 2007; Fulde et al., 2013). The aim of the studies presented in this thesis was to identify novel virulence factors of Streptococcus agalactiae or GBS that might be involved in binding to host factors, particularly Plg. First, a novel protein (Gbs0428 or PbsP) was identified by proteomics analysis of the GBS exoproteome and found to display two SSURE domains (Bumbaca et al., 2004), homologous with those of the previously characterized Plasminogen and fibronectin binding protein B (PfbB, also called PavB) of Streptococcus pneumoniae (Papasergi et al., 2010). Next, the role of Gbs0428 in the contest of GBS pathogenesis was investigated. After showing that Gbs0428 is a cell-wall-anchored surface protein that binds Plg, it was found that this adhesin is expressed by isolates belonging to all of the main GBS lineages, including strains of the hypervirulent clonal complex 17 (CC17), which is responsible for a large number of neonatal GBS infections, particularly meningitis cases. In the context of the CC17 prototype BM110 strain, PbsP was found to be markedly upregulated in vivo. PbsP was also found to bind Plg largely through the interaction between lysine-binding sites in the kringle 4 domain of Plg with a novel protein domain that was named MK-rich region. Moreover, PbsP-mediated Plg binding conferred proteolytic activity to GBS surface, which ensured GBS transmigration across endothelial cells and colonization of the brain. All together these data indicate that PbsP has an important role in the pathogenesis of GBS infections and might represent a target in alternative strategies to control GBS infection.
GBS, plasminogen binding protein, SSURE repeat, CC17 strains
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11570/3105235
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