Unraveling the mouse model of Staphylococcus aureus bacteremia and sepsis: a systematic approach to better characterize host/pathogen interactions

Staphylococcus aureus is a pathobiont whose primary human reservoirs are nares, pharynx, intestines, and skin. When specific conditions in the host are altered, it can cause a wide variety of human diseases, including bacteremia and sepsis. Preclinical in vivo models mimicking the most severe S. aureus infections in humans have been used to develop treatments against this pathogen. This study aims to better characterize a murine model of S. aureus bacteremia and sepsis, offering a new and more comprehensive view of the complex interactions between S. aureus and the host while better reflecting human disease dynamics. We investigated the kinetics of bacteria in blood, kidneys, and liver after infection with four strains representative of epidemiologically relevant S. aureus clonal lineages. After intravenous infection, bacteria progress through three major pathogenesis phases: (i) colony-forming units counts in blood decrease rapidly within 1–2 h as bacteria are captured by the liver, the first line of defense against blood-borne bacteria; (ii) mice begin to show signs of acute disease, and bacteria disseminate to the kidneys where they grow quickly, reaching the peak in 1–2 days; (iii) bacteria establish an equilibrium with the host, forming abscesses in the kidneys while persisting in low numbers in the blood. These phases are common to all the tested S. aureus strains, although some strain-specific peculiarities have also been identified. Our findings could help improve understanding of host-pathogen interactions in S. aureus infections and their implications for human health, potentially laying the groundwork for developing novel preventive and therapeutic strategies.