Biology subjects

Bjorck, L.

Publications and source records attributed to Bjorck, L..

3 recordsLinked to original sources

bioRxiv2025

Streptococcus pyogenes nuclease A interferes with host complement functions

Bacterial pathogens deploy diverse virulence factors to subvert host immunity, yet the molecular details of these interactions often remain unresolved. Here, we investigate the structure and host interactome of the Streptococcus pyogenes nuclease A (SpnA). We characterized the structure and dynamics of SpnA using hydrogen-deuterium exchange mass spectrometry and single-particle electron cryo microscopy, yielding the first structural insights to this protein. This allowed us to identify an additional oligonucleotide-binding domain whose flexible structure may play an important function in the nucleolytic activity of SpnA. Affinity-pulldown mass spectrometry identified the complement system membrane attack complex C5b67 components as key interactors in human plasma. Cross-linking mass spectrometry combined with integrative modeling identified the direct binding interfaces between SpnA and C5b67. These interfaces are highly conserved among genetically diverse S. pyogenes strains. The interaction between SpnA and C5b67 is suggested to prevent the assembly of a functional membrane attack complex. Taken together, our findings uncover a novel function of SpnA in complement inhibition and identifies new potential targets to prevent and treat S. pyogenes infections.

microbiology↗

bioRxiv2021

Bacterial clearance caused by a single anti-M protein antibody simultaneously binding two separate epitopes

Group A streptococci have evolved multiple strategies to evade human antibodies, making it challenging to create effective vaccines or antibody treatments. Here, we have generated antibodies derived from the memory B cells of an individual who had successfully cleared a group A streptococcal infection. The antibodies bind with high affinity in the central region of the surface-bound M protein. Such antibodies are typically non-opsonic. However, one antibody could effectively promote vital immune functions, including phagocytosis and in vivo protection. Remarkably, this antibody primarily interacts through a bivalent dual-Fab cis mode, where the Fabs bind to two distinct epitopes in the M protein. The dual-Fab cis binding phenomenon is conserved across different groups of M types. In contrast, other antibodies binding with normal single-Fab mode to the same region can not bypass the M proteins virulent effects. A broadly binding, protective monoclonal antibody could be a candidate for anti-streptococcal therapy. Our findings highlight the concept of dual-Fab cis binding as a means to access conserved, and normally non-opsonic regions, for protective antibody targeting.

immunology↗

bioRxiv2020

Vaccine-induced, but not natural immunity, against the Streptococcal Inhibitor of Complement protects against invasive disease

Highly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We therefore propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full length SIC permits development of protective antibodies against all SIC domains.

microbiology↗