Evaluation of the PBP2 transglycosylase region of Staphylococcus aureus as a target for immunotherapeutic approaches.

Autor: Corrêa Argondizzo AP; Recombinant Technology Laboratory, Technological Development Department, Instituto de Tecnologia Em Imunobiológicos BioManguinhos FIOCRUZ, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Saraiva FB; Recombinant Technology Laboratory, Technological Development Department, Instituto de Tecnologia Em Imunobiológicos BioManguinhos FIOCRUZ, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Almeida M; Instituto Oswaldo Cruz - IOC FIOCRUZ, Avenida Brasil 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Nunes Peres AM; Assessoria Clínica, Instituto de Tecnologia Em Imunobiológicos BioManguinhos FIOCRUZ, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil., Moreno Senna JP; Recombinant Technology Laboratory, Technological Development Department, Instituto de Tecnologia Em Imunobiológicos BioManguinhos FIOCRUZ, Avenida Brasil, 4365, Manguinhos, Rio de Janeiro, RJ, 21040-900, Brazil. Electronic address: jprocopio@bio.fiocruz.br.
Jazyk: angličtina
Zdroj: Microbial pathogenesis [Microb Pathog] 2021 Aug; Vol. 157, pp. 105000. Date of Electronic Publication: 2021 May 25.
DOI: 10.1016/j.micpath.2021.105000
Abstrakt: 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.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: