Investigating Staphylococcus aureus Intracellular Tactics and Nanomedicine Solutions

The rapid spread of antimicrobial resistance (AMR) jeopardizes the effectiveness of modern medicine in treating infections. This thesis describes the use of nanomedicine in addressing the clinical challenges posed by multi-drug resistant Staphylococcus aureus bacteria. Nanoparticles possess unique properties that can be engineered for various biomedical applications, including the potential bypass of antibiotic resistance mechanisms. Two central aims of the presented research are to gain a better understanding of S. aureus interactions with human host cells, and to investigate a nanomedicine-based solution for targeting intracellular S. aureus infections.The thesis begins by introducing S. aureus and the epidemiology of S. aureus infections, detailing this bacterium’s ability to develop AMR, to invade different tissues and to form biofilms. Several intracellular infection models are presented, along with potential methods to identify infected cells, thereby providing a better understanding of how S. aureus interacts with and persists inside host cells. The results support the identification of potential nanomedicinal strategies to treat intracellular S. aureus infections. The second part of the thesis describes the feasibility of using gold nanoparticles as carriers for antibiotic delivery to target intracellular S. aureus bacteria, as well as planktonic or biofilm-resident bacteria. Altogether, the results presented in this thesis show that a multi-pronged approach is needed to combat AMR. It is concluded that knowledge gained from further fundamental research into the biology of microbes and their interactions with host cells will be instrumental for developing new strategies to combat AMR and to ensure the continued effectiveness of antimicrobial treatments