Caracterización del sistema sensorial de dos componentes de Staphylococcus aureus

Abstract

During the course of the thesis we have participated in the development of two potential complementary therapies against S. aureus. The first strategy was carried out within the framework of the project ‘New strategies to control nosocomial infections’ (RTC-2015-3184-1) and we have participated in the screening of a collection of FDA’s approved drugs (Prestwick collection) as new antimicrobial agents. The objective was to repurpose one the compounds as a new drug against S. aureus, in this case the target of the screening was the TCS GraRS. The second strategy is presented in the fourth chapter of the thesis. The goal was to develop a potential complementary therapy against S. aureus based on two different immunetherapy strategies: monoclonal antibodies and nanobodies. For that, we have focused on the HK of S. aureus and in particular the antibodies were developed against the ligand-binding domain (LBD) of the HK from WalRK. We have selected this target because WalRK is the only essential TCS of S. aureus and besides, assays performed with serum from patients with an S. aureus infection showed an immunogenic response against the LBD. We have been able to obtain both, the monoclonal antibody and also different nanobodies against the LBD region of WalK able to recognize the peptide in vitro and in vivo. Unexpectedly, incubation of S. aureus with various nanobodies promoted instead of inhibited bacterial growth. These surprising results indicate that nanobodies can modify the activity of HKs and as a consequence, interfere with the signal transduction system.