Streptococcus agalactiae Non-Pilus, Cell Wall-Anchored Proteins: Involvement in Colonization and Pathogenesis and Potential as Vaccine Candidates

Abstract

Group B Streptococcus (GBS) remains an important etiological agent of several infectious diseases including neonatal septicemia, pneumonia, meningitis, and orthopedic device infections. This pathogenicity is due to a variety of virulence factors expressed by Streptococcus agalactiae. Single virulence factors are not sufficient to provoke a streptococcal infection, which is instead promoted by the coordinated activity of several pathogenicity factors. Such determinants, mostly cell wall-associated and secreted proteins, include adhesins that mediate binding of the pathogen to host extracellular matrix/plasma ligands and cell surfaces, proteins that cooperate in the invasion of and survival within host cells and factors that neutralize phagocytosis and/or modulate the immune response. The genome-based approaches and bioinformatics tools and the extensive use of biophysical and biochemical methods and animal model studies have provided a great wealth of information on the molecular structure and function of these virulence factors. In fact, a number of new GBS surface-exposed or secreted proteins have been identified (GBS immunogenic bacterial adhesion protein, leucine-rich repeat of GBS, serine-rich repeat proteins), the three-dimensional structures of known streptococcal proteins (αC protein, C5a peptidase) have been solved and an understanding of the pathogenetic role of “old” and new determinants has been better defined in recent years. Herein, we provide an update of our current understanding of the major surface cell wall-anchored proteins from GBS, with emphasis on their biochemical and structural properties and the pathogenetic roles they may have in the onset and progression of host infection. We also focus on the antigenic profile of these compounds and discuss them as targets for therapeutic intervention.

Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors

“…Our in vitro adhesion assays assessing the -dependent mechanism support this conclusion. Thus, CEACAM1 and CEACAM5 expand the repertoire of human cell surface proteins that GBS may employ for adhesion (Pietrocola et al, 2018). Further work is required to determine the consequences of the interaction between -IgI3 and CEACAM beyond cell lines.…”

“…Cellular adhesion to mucosal surfaces is the first critical step preceding infection (Patras & Nizet, 2018). Bacteria colonization is a multifactorial process that requires expression of adhesins that target extracellular matrix (ECM) constituents and/or host cell receptors (Pietrocola et al, 2018; Shabayek & Spellerberg, 2018). Indeed, GBS express a diverse array of surface adhesins and the exact repertoire varies from strain to strain, reflective of high plasticity of the GBS genome (Chen, 2019;Gori et al, 2020;Tettelin et al, 2005).…”

“…The mechanisms underpinning binding to ECM constituents are well-defined, and include targeting fibronectin, laminin and vitronectin (Deng et al, 2019;Spellerberg et al, 1999;Hull et al;Banerjee et al, 2011). In contrast, our knowledge of the mechanisms that GBS utilizes to directly promote host cell adhesion is limited (Patras & Nizet, 2018;Bolduc & Madoff, 2007;Pietrocola et al, 2018). In particular, the host receptors targets of several putative adhesins, including Rib and Sip proteins (Stålhammar-Carlemalm et al, 1993;Brodeur et al, 2000), remain uncharacterized.…”

“…In particular, the host receptors targets of several putative adhesins, including Rib and Sip proteins (Stålhammar-Carlemalm et al, 1993;Brodeur et al, 2000), remain uncharacterized. To develop vaccine or anti-bacterial strategies that interfere with mucosal colonization, insights into the full adhesin-receptor interaction repertoire is required (Pietrocola et al, 2018;Larsson et al, 1996;Heath, 2016;Michel et al, 1992).…”

Novel structure of the N-terminal helical domain of BibA, a group B streptococcus immunogenic bacterial adhesin

“…The sequence of BibA is highly conserved in all clinical isolates, with the N-terminal domain being identical and the prolinerich region showing 98-100% similarity (Santi, Maione et al, 2009). The putative N-terminal helical domain protects GBS from phagocytic killing by attaching to the complement inhibitor C4b-binding protein (C4BP; Santi et al, 2007;Pietrocola et al, 2018). BibA protein was shown to be highly expressed on the GBS surface at pH 7.0 and to a lower extent at pH 5.5 (Santi, Grifantini et al, 2009), and such pH-regulated BibA expression is fully reversible upon exposure to a new pH environment.…”