Anti-SpA Antibody Discovery Service

With integrated antibody development as well as engineering techniques and advanced antibody-related research platform, Creative Biolabs provides antibody customization services for Staphylococcus aureus(S. aureus) protein A (SpA) to help our clients make great advances in their projects.

SpA Function

S. aureus is a leading cause of human soft tissue infections and bacterial sepsis. Fatal S.aureus infections are often associated with bacteremia, having a 65-70% mortality rate. Up to one-half of Staphylococcal pneumonia isolates are classified as Methicillin-Resistant S. aureus (MRSA). Search for alternative options to treat or prevent serious S. aureus infections attracts world-wide concerns due to the increasingly serious MRSA infection. As a key virulence factor on the surface of S. aureus, SpA enables S. aureus to evade innate and adaptive immune responses. SpA tightly binds to the Fc portion of human and animal immunoglobulin (Ig), neutralizing effector function and providing S. aureus with protection from opsonophagocytic killing.

Fig.1 Mechanisms of SpA-mediated immune evasion (Left panel).^1,2

SpA (red crescent shape) present on the surface of S. aureus or SpA that is freely secreted binds the Fc region of the antibody, thereby preventing normal phagocytosis (right panel). Alternatively, SpA binds the Fab regions of the B-cell receptor (lower left panel), which induces B-cell death and prevents the production of an antibody specific for S. aureus, PMN, and polymorphonuclear leukocyte.

Protein Structure

Five 56- to 61-residue Ig binding domains (IgBDs) of SpA are displayed on the bacterial surface, and the amino acid sequence of IgBDs is highly conserved. Each IgBD binds the Fcγ region of human IgG 1, 2 and 4 with high affinity.

SpA consists of several domains. The C-terminal half of the protein is used to target the protein for attachment on the extra-cellular surface to the peptidoglycan cell wall via the LPXTG motif. The low complexity and probably unstructured Region X domains are designed to span the thick carbohydrate-rich covering on the bacterium. Thus, the N-terminal half extends past this covering and is available to bind to the host proteins described above.

Antibody-based Therapy

Monoclonal antibodies (mAbs) offer the possibility to investigate the biological characteristics of humoral adaptive immune responses to microbial surface products. Staphylococcal infections in humans or mice do not elicit protein A-specific humoral immune responses, but immunization with protein A variants, such as SpAKKAA molecule, elicits humoral immune responses in mice and rabbits. SpAKKAA is nontoxigenic protein A molecule with amino acid substitution at specific sites. These antibodies are elicited by SpA variants cross-react with wild-type SpA and provide protection against Staphylococcal disease.

Features

• Fast turnaround time and competitive pricing
• Innovative and diversified platforms
• Customized and comprehensive service

At present, the combination of antibiotic with anti-bacteria mAbs could form antibody-antibiotic conjugate (AAC) complex and expand the therapeutic options, reduce the duration of therapy. With the novel technology platform and professional scientist team, Creative Biolabs gets ready to provide you with the best antibodies for AAC development. If you are interested in the service we provide, please don’t hesitate to contact us for more details.

References

1. Kobayashi, Scott D., and Frank R. DeLeo. "Staphylococcus aureus protein A promotes immune suppression." MBio 4.5 (2013): 10-1128.
2. Distributed under Open Access License CC BY 4.0, without modification.