Identification of SbnA and IsdB Inhibitors to Fight Antimicrobial Resistance

Antimicrobial resistance (AMR) is a growing global public health crisis, occurs when bacteria evolve and no longer respond to antibiotics. Staphylococcus aureus, a pathogenic bacterium, is particularly concerning as it has developed strains resistant to multiple antibiotics, including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant S. aureus (VRSA). Iron is a crucial nutrient required by S. aureus, but humans have developed a mechanism called nutritional immunity (NI) to limit bacterial access to iron. However, the pathogen has evolved mechanisms to overcome iron limitation, including the production of siderophores and the scavenging of heme via hemophores. This research project focuses on targeting crucial proteins involved in S. aureus iron acquisition systems, specifically SbnA, responsible for siderophore staphyloferrin B biosynthesis, and IsdB, a hemophore involved in heme uptake from hemoglobin. Understanding the molecular mechanisms of these proteins and their interactions with substrates can provide insights into the development of novel antimicrobial therapies. In this thesis, computational techniques such as structure-based virtual screening and molecular docking simulations were employed to identify potential drug candidates. By using these techniques, it was possible to analyze thousands of compounds in a relatively short span of time, identifying potential hit compounds.