β-GlcNAc-WTA mAb Development

Creative Biolabs is an antibody discovery and engineering pioneer and we now focus on developing highly specific monoclonal antibodies (mAbs) against β-GlcNAc-WTA with our elaborate platform.

Antibiotics, as nature’s gifts, have benefit human health for years. However, many common infections nowadays are becoming resistant to antibiotics worldwide, resulting in prolonged illnesses and increasing deaths. A novel therapeutic strategy, antibody-antibiotic conjugate (AAC) has emerged as a hopeful approach for curing the infection of antibiotic-resistant strains, based on the unique specificity of the antibody to achieve the target delivery of antibiotic.

Wall Teichoic Acid

Gram-positive cell wall mainly contains three parts, peptidoglycan, teichoic acid, and wall-associated protein. Among them, teichoic acids are located in the outer layer, including both wall teichoic acids (WTAs) which are covalently attached to peptidoglycan, and lipoteichoic acids (LTAs) which are anchored in the bacterial membrane via a glycolipid. WTAs are involved in pathogenesis and play key roles in β-lactam resistance in Methicillin-Resistant Staphylococcus aureus (MRSA). WTAs compose of phospho-ribitol repeating units further modified by either α- or β-O-linked N-acetylglucosamine (GlcNAc) sugars which are mediated by TarM or TarS glycosyltransferases, respectively. However, expression of the α-O-linked GlcNAc was absent on some S. aureus isolates.

Fig.1 Teichoic acid polymers are located within the gram-positive cell wall. (Brown, 2013)

WTA Antibodies against Staphylococcus aureus (S. aureus) Infection

S.aureus is a major cause of bacterial infection in humans worldwide and represents a major health concern in hospital and community settings. As a structural component of the cell wall, WTA is highly abundant and conserved on S. aureus in vitro and during infection, as well as absent from human cells. As reported, there are nearly 50 000 β-GlcNAc-WTA mAb antibody-binding sites presenting on a single S. aureus bacterium. Additionally, the TarS glycosyltransferase is conserved in all MRSA, which is responsible for appending β-GlcNAc onto ribitol phosphate. An AAC that combines advantages of β-GlcNAc-WTA mAb and dmDNA31(4-dimethylamino piperidino-hydroxybenzoxazino rifamycin) has been proved to be effective against S. aureus infection.

Fig.2 Anatomy of the THIOMABTM antibody-antibiotic conjugate (AAC). Each AAC consists of two molecules, dmDNA31 antibiotics (red) linked to each of the light chains of the b-GlcNAc-WTA mAb via a linker (blue). Within acidic intracellular vesicles, lysosomal proteases cleave the amide bond (arrowhead) at the C terminus of citrulline to release active dmDNA31 to kill bacteria. (Mariathasan, 2017)

Features

• High-affinity and high-specificity mAbs
• The comprehensive technical platform, including Hybridoma Platform, B-Cell Sorting Platform, Phage Display Platform, Membrane Protein Platform...
• Cost-effective
• Customized service

Creative Biolabs provides various antibody development services and we are capable of providing you high-quality mAbs against β-GlcNAc-WTA for your AAC development. Please feel free to contact us for more information and a detailed quote.

References:

1. Brown, S.; et al. (2013). Wall teichoic acids of gram-positive bacteria. Annual review of microbiology, 67, 313-336.
2. Mariathasan, S.; Tan, M. W. (2017). Antibody–antibiotic conjugates: a novel therapeutic platform against bacterial infections. Trends in molecular medicine, 23(2), 135-149.