Evaluation of the PBP2 transglycosylase region of Staphylococcus aureus as a target for immunotherapeutic approaches.
2021
Infections caused by Staphylococcus aureus are increasingly prevalent, and treatment has become more difficult
due to the emergence of strains that are resistant to multiple drugs, such as methicillin-resistant Staphylococcus
aureus (MRSA). Penicillin-binding proteins (PBPs) are essential enzymes in peptidoglycan biosynthesis. Only
found in bacteria, they are an excellent target for the development of bacterial control strategies. S. aureus has 4
PBPs, and only PBP2 has transglycosylation activity, making it a good model to evaluate whether the inactivation
of the transglycosylase domain (PBP2t) could lead to bacterial death. (His6)-tagged PBP2t was purified from the
E. coli cell lysate using Ni-charged resin, and ELISA and immunoblotting assays demonstrated that PBP2t is
immunogenic. Flow cytometry analysis was performed to verify the binding of polyclonal antibodies to the
bacterial cell surface. In order to verify the ability to provide protection, immunized mice were challenged with a
sublethal dose of MRSA, and the bacterial loads in kidneys and spleen were evaluated. A reduction of 2–2.5 logs
was seen in organs from immunized mice compared with the negative controls in two independent assays (p <
0.01). Our results demonstrate that the PBP2t is a promising target for the development of novel antimicrobial
strategies, but further testing should be performed to validate the protection conferred by immunization with this
protein.
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