Anti-IsdB Antibody Development

As a leading company that provides antibody services, Creative Biolabs is committed to offering integrated antibody discovery and development services for clients all over the world. Creative Biolabs now provides antibody customization services for Staphylococcus aureus (S. aureus) iron-regulated surface determinant B (IsdB) by advanced platforms to help your projects. Our professional scientist team has extensive experience in antibody development and engineering,  and we are capable of providing customized service to meet every client's specific demands.

IsdB Introduction

S.aureus is a human pathogen that causes invasive and recurring infections, including endocarditis, osteomyelitis, and skin and soft tissue infections. IsdB is a conserved protein expressed on the cell surface of S. aureus in iron limited environments, with an molecular weight (MW) of approximately 72 kDa. The protein is up-regulated under iron-restricted conditions and functions to capture and import heme iron from hemoglobin. IsdB also promotes bacterial invasion into human cells.

FFig.1 IsdB is exposed on the cell surface. (Schneewind, 2012)

Protein Structure

Free iron is not available in most environments, so organisms need high-affinity systems to acquire iron. S.aureus employs the iron-responsive surface determinant (Isd) system as its primary heme-iron uptake pathway. IsdB and IsdH are anchored to the cell wall by a mechanism requiring a C-terminal sorting signal. Hemoglobin or hemoglobin-hemoglobin complexes are bound by Near iron-Transport (NEAT) domains within IsdB or IsdH. Heme is stripped from the host proteins and transferred between NEAT domains through IsdA and IsdC to the membrane transporter IsdE and IsdF for internalization. Once internalized, heme can be degraded by IsdG or IsdI, thus liberating iron for the organism.

Fig.2 Schematic representation of the Isd system heme transport components in S. aureus. (Tiedemann, 2008)

Antibody-based Therapy

As reported, monoclonal antibodies (mAbs) against IsdB have opsonophagocytic killing activity and observably enhanced survival in the murine sepsis model in Balb/c mice. Antibodies against IsdB are thought to block heme-iron scavenging during infection. Besides, IsdB can induce human protective CD4(+) T-cell immune response. IsdB is currently being investigated for clinical efficacy against S. aureus infection, and the activity of IsdB specific antibody supplements the growing body of evidence to support targeting this antigen for therapy development.

Fig.3 IsdB surface protein and heme-iron scavenging of S. aureus. (Missiakas, 2016) Diagram illustrating the physiological role of IsdB in scavenging heme-iron from host hemoglobin and transferring this nutrient across the bacterial envelope, followed by iron release from heme in the bacterial cytoplasm.

Considering the prevalence of drug-resistant bacteria, a possible strategy to improve the current situation is to combine an approach designed to enhance the host immune response with antibiotic therapy against the drug-resistance pathogen. Accordingly, Antibody-antibiotic conjugate( AAC) has the advantages of both antibiotic and anti-bacteria mAbs, which could expand the therapeutic options, reduce the duration of therapy. With the novel technology platform and professional antibody experts, Creative Biolabs is capable of providing you with the best antibody development services to help your AAC project. If you are interested in the anti-IsdB antibody development services that we provide, please feel free to contact us for more details.

References

1. Schneewind, O.; Missiakas, D. M. (2012). Protein secretion and surface display in Gram-positive bacteria. Phil. Trans. R. Soc. B, 367(1592), 1123-1139.
2. Tiedemann, M. T.; et al. (2008). Iron acquisition by the haem-binding Isd proteins in Staphylococcus aureus: studies of the mechanism using magnetic circular dichroism. Biochemical Society Transactions, 36(6), 1138-1143.
3. Missiakas, D.; Schneewind, O. (2016).Staphylococcus aureus vaccines: Deviating from the carol. Journal of Experimental Medicine, 213(9):1645-1653.

For Research Use Only. NOT FOR CLINICAL USE.