The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates

Abstract

Lethal meningitis triggered by the hypervirulent group B streptococcus clone ST-17 is mediated by a novel surface protein called HvgA.

Concepts and Mechanisms: Crossing Host Barriers

“…Among the GBS clones, ST-17 is strongly associated with meningitis in infants. It has been shown that a ST-17-specific surface-anchored protein called hypervirulent GBS adhesin (HvgA) is required for intestinal colonization and translocation across the intestinal barrier and the blood-brain barrier (BBB), leading to meningitis (Tazi et al 2010). The mechanism by which the ST-17 clone crosses the intestinal barrier is still unknown.…”

“…Many studies have focused on the identification of bacterial and host components involved in microbial interactions with the BBB (Kim 2008). Critical bacterial components have been discovered by screening random mutant libraries (Badger et al 2000;Doran et al 2005), analyzing bacterial transcription profiles during infection (Dietrich et al 2003;Teng et al 2005), and using bioinformatic approaches for whole genome comparisons (Uchiyama et al 2009;van Sorge et al 2009;Tazi et al 2010). Bacterial pili, or fimbriae, have emerged as a common class of adhesins used by many meningeal pathogens, such as E. coli K1 (Teng et al 2005), GBS (Maisey et al 2007;van Sorge et al 2009), and N. meningitides (Kirchner and Meyer 2005) to initiate attachment to brain endothelium.…”

“…Bacterial pili, or fimbriae, have emerged as a common class of adhesins used by many meningeal pathogens, such as E. coli K1 (Teng et al 2005), GBS (Maisey et al 2007;van Sorge et al 2009), and N. meningitides (Kirchner and Meyer 2005) to initiate attachment to brain endothelium. Other well-characterized or recently described bac- terial components such as CbpA and NanA, a surface anchored sialidase, in S. pneumonia (Ring et al 1998;Uchiyama et al 2009), lipoteichoic acid and HvgA in GBS (Doran et al 2005;Tazi et al 2010), type1 fimbriae, OmpA and ibeA/B in E. coli K1 (Prasadarao et al 1999a,b;Teng et al 2005), promote brain endothelial cell attachment and subsequent cellular penetration. Separately, bacterial toxins play an important role in microbial interactions with the BBB.…”

Sequence type 1 group B Streptococcus , an emerging cause of invasive disease in adults, evolves by small genetic changes

“…A seven-gene multilocus sequence typing (MLST) allows for the classification of the majority of GBS strains isolated from humans into five major clonal complexes (CCs) with a recent study by Da Cunha et al showing that the major GBS CCs are primarily derived from a limited number of tetracycline-resistant clones, suggesting a key role of tetracycline resistance in GBS strain emergence (10,11). CC-17 GBS strains have been particularly well studied given their role as the major cause of severe, invasive infant disease (10,12). In contrast, serotype V strains cause a larger percentage of invasive disease in nonpregnant adults compared with neonates (13)(14)(15).…”

Méningite néonatale à streptocoque du groupe B

“…L'un de ces variants, BibA, avait été précédemment étudié et sa contribution à l'adhésion de streptocoques du groupe B aux cellules épithéliales avait été montrée [9]. L'autre variant, strictement spécifique des souches ST-17 [7,8], a été désigné HvgA (hypervirulent group B streptococcus adhesin) et nous avons exploré son rôle dans l'infection néonatale au streptocoque du groupe B en combinant des approches in vitro et in vivo [10]. Figure 1B).…”