1) therapies to combat intracellular bacteria through high-content microscopy screening of natural compounds
Bacterial infections, particularly those caused by multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), pose a serious global public health threat. The intracellular colonization of S. aureus contributes to treatment failure, as conventional antibiotics do not reach effective intracellular concentrations. Due to increasing antimicrobial resistance, host-directed therapy (HDT) has emerged as a promising alternative by targeting host pathways essential for bacterial survival. In this context, natural products represent a rich source of bioactive molecules for HDT, offering vast chemical diversity and polypharmacological properties.
This project will conduct a large-scale, microscopy-based phenotypic screen of 2,000 natural products derived from Brazilian biodiversity to identify bioactive candidates against intracellular S. aureus. Selected compounds will be validated in different human cell types and clinical S. aureus isolates. Mechanisms of action will be investigated using Cell Painting, an innovative multiparametric method for morphological profiling. The most promising compounds will be tested in a murine model of staphylococcal sepsis.
The project aims to identify new antimicrobial compounds, uncover novel pathogen–host interactions and expand the technological infrastructure of the Host Institution. In the medium and long term, the results may directly impact the development of alternative and more effective antimicrobial therapies.