Anti-PBP-2a Antibody Development

As a leading provider of high-quality antibody for global academic and industrial clients, Creative Biolabs has years of experience in the discovery and development of antibodies against various targets. Here, Creative Biolabs provides antibody customization services for Methicillin-Resistant Staphylococcus aureus (MRSA) PBP-2a protein based on our advanced technology platform to help proceed with your projects.

Mechanism of Resistance in Staphylococcus aureus (S. aureus)

MRSA is a multidrug-resistant bacteria that causes serious infections worldwide. Resistance is conferred by the acquisition of a non-native mecA gene encoding a penicillin-binding protein (PBP-2a), with a significantly lower affinity for β-lactams. In the normal case, the native PBP involves in the synthesis of staphylococcal cell wall peptidoglycan and this process could be inhibited by β-lactam antibiotics. However, in the presence of high concentrations of β-lactam antibiotics, PBP-2a can continue the cell-wall bio-synthesis when native PBP bind to the β-lactam antibiotics with higher affinity.

Fig.1 Model for the mecA induction by MecR1-MecI-MecR2. (Arêde, 2012) In the presence of a β-lactam antibiotic, MecR1 is activated and rapidly induces the expression of mecA and mecR1-mecI-mecR2. The anti-repressor activity of MecR2 is essential to sustain the mecA induction since it promotes the inactivation of MecI by proteolytic cleavage. In the absence of β-lactams, MecR1 is not activated and a steady state is established with stable MecI-dimers bound to the mecA promoter and residual copies of MecR1 at the cell membrane.

PBP-2a Protein

The high-molecular-mass PBP of bacteria catalyzes in separate domains the transglycosylase and transpeptidase activities required for the biosynthesis of the peptidoglycan polymer that comprises the bacterial cell wall. In S. aureus, there are four native PBPs, PBP1, PBP2, PBP3, and PBP4. The fifth PBP-2a, a 78 kDa protein, is a unique feature and located externally to the membrane of all MRSA strains. The expression of PBP-2a is the basis for the broad clinical resistance to the β-lactam antibiotics by MRSA. The PBP-2a of MRSA is resistant to β-lactam acylation and successfully catalyzes the DD-transpeptidation reaction necessary to complete the cell wall. The PBP-2a that confers resistance in all β-lactam agents by having a low binding affinity towards β-lactam antibiotics and enabling staphylococci to survive even upon exposure to high concentrations of β-lactam agents, was considered a prime target for MRSA inhibition among other PBPs. Basically, PBP-2a consists of four broad domains, transmembrane anchor, N-terminal extension, non-penicillin-binding domain, and C-terminal transpeptidase domain.

Fig.2Structure of PBP-2a. (Rani, 2014)

Antibodies of PBP-2a

Anti-PBP-2a monoclonal antibodies (mAbs) have been usedwidely in vitro diagnosis of MRSA strains. For example, literature reports that a specific mAb (patent application number WO/2011/017791) against MRSA PBP-2a was obtained by Bio-Manguinhos using the hybridoma technology. This mAb can be applied in the manufacture of in vitro diagnosis (IVD) products. Passive immunization with this specific mAbs combined with antibiotics is likely to provide enhanced protective efficacy against MRSA infections.

Besides the expertise in antibody design and engineering, Creative Biolabs is also dedicated to the areas of antibody-antibiotic conjugate (AAC) complex by conjugating monoclonal antibodies with various antibiotics. With more than 10 years of experience in immunology, bio-conjugation chemistry and molecular biology, the science team at Creative Biolabs can provide customers with comprehensive services from AAC design to the production of the fully conjugated complex. Equipped with novel technology platform and professional experiment services, Creative Biolabs now gets ready to provide you with the best antibody services about PBP-2a protein. Please feel free to contact us for more details.

References

1. Arêde, P.; et al. (2012). The anti-repressor MecR2 promotes the proteolysis of the mecA repressor and enables optimal expression of β-lactam resistance in MRSA. PLoS Pathogens. 8(7), e1002816.
2. Rani, N.; et al. (2014). Quercetin 3-O-rutinoside mediated inhibition of PBP2a: computational and experimental evidence to its anti-MRSA activity. Molecular BioSystems. 10(12): 3229-3237.

For Research Use Only. NOT FOR CLINICAL USE.