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

Abstract

BibA, a group B streptococcus (GBS) surface protein, has been shown to protect the pathogen from phagocytic killing by sequestering a complement inhibitor: C4b-binding protein (C4BP). Here, the X-ray crystallographic structure of a GBS BibA fragment (BibA126–398) and a low-resolution small-angle X-ray scattering (SAXS) structure of the full-length N-terminal domain (BibA34–400) are described. The BibA126–398 fragment crystal structure displayed a novel and predominantly helical structure. The tertiary arrangement of helices forms four antiparallel three-helix-bundle-motif repeats, with one long helix from a bundle extending into the next. Multiple mutations on recombinant BibA34–400 delayed the degradation of the protein, and circular dichroism spectroscopy of BibA34–400 suggested a similar secondary-structure composition to that observed in the crystallized BibA126–398 fragment. A model was generated for the 92 N-terminal residues (BibA34–125) using structural similarity prediction programs, and a BibA34–400 model was generated by combining the coordinates of BibA34–126 and BibA126–398. The X-ray structure of BibA126–398 and the model of BibA34–400 fitted well into the calculated SAXS envelope. One possible binding site for the BibA N-terminal domain was localized to the N-terminal CCP (complement-control protein) domains of the C4BP α-chain, as indicated by the decreased binding of BibA to a ΔCCP1 C4BP α-chain mutant. In summary, it is suggested that the GBS surface protein BibA, which consists of three antiparallel α-helical-bundle motifs, is unique and belongs to a new class of Gram-positive surface adhesins.

Immunogenic Proteins of Group B Streptococcus—Potential Antigens in Immunodiagnostic Assay for GBS Detection

“…The protein consists of the N-end α-helix rich domain, proline-rich region, LPXTG cell-wall anchoring motif, and is composed of 594 amino acids. Due to its N-terminal helical domain, which consists of three antiparallel α-helical-bundle motifs, it is considered as unique, and thus is qualified to a new class of Gram-positive surface adhesins [55]. This protein is identified on the surface of S. agalactiae strains, but interestingly, it is also present in GBS culture supernatants [56,57].…”

Characterization and virulence of Streptococcus agalactiae deficient in SaeRS of the two-component system

“…We measured the mRNA expression of some colonization and invasion-related genes by RT-qPCR. Of these, srr-1 , bibA , and bac genes are involved in the adhesion between S. agalactiae and host cells ( Sundaresan et al, 2011 ; Souza et al, 2013 ; Manne et al, 2020 ), while hylB and fbsB genes are involved in the infection and spread of GBS in host cells ( Pritchard et al, 1994 ; Gutekunst et al, 2004 ; Bobadilla et al, 2021 ). The decreased mRNA expression of these adhesion and invasion factors may be the reason for the in vivo competitive ability of mutant strain.…”

Immunization with Multiple Virulence Factors Provides Maternal and Neonatal Protection against Group B Streptococcus Serotypes

“…Recombinant SrtA (amino acids 82 to 247) and Srr2 (amino acids 192 to 543) were cloned into the pET28a vector as previously described [ 19 , 37 ]. Recombinant FbsB (amino acids 19 to 628) and BibA (amino acids 34 to 471) were cloned into the pCold-SUMO vector [ 16 , 18 ]. For CspA and ScpB, mutations were generated to remove their toxic enzymatic activity.…”

“…There is increased awareness of the involvement of GBS protein antigens not only in immunity but also in pathogenicity [ 14 ]. Clinical GBS strains have evolved a wide variety of virulence factors [ 15 ], including adhesins that mediate GBS colonization of the vaginal tract, enabling transmission to newborns to cause EOD [ 16 ]. Other virulence factors, such as FbsB and ScpB, can facilitate GBS invasion of various tissues, damaging the tissue structure, which leads to dysfunction of human organs [ 17 , 18 ].…”