Unraveling the mouse model ofbacteremia and sepsis: a systematic approach to better characterize host/pathogen interactions.

Abstract

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. Preclinicalmodels mimicking the most severeinfections in humans have been used to develop treatments against this pathogen. This study aims to better characterize a murine model ofbacteremia and sepsis, offering a new and more comprehensive view of the complex interactions betweenand 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 relevantclonal 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 testedstrains, although some strain-specific peculiarities have also been identified. Our findings could help improve understanding of host-pathogen interactions ininfections and their implications for human health, potentially laying the groundwork for developing novel preventive and therapeutic strategies.IMPORTANCEOur work provides new insights into the interaction betweenand the host in a mouse model of bloodstream infection and sepsis. We found similarities between findings in the mouse model and human disease, underscoring the importance of using this laboratory host to study new therapeutic and preventive interventions. The comprehensive approach we used, utilizing several epidemiologically relevantclones and two distinct mouse strains, enhances the relevance of our results and sheds light on the complex interaction between this human pathogen and a widely used laboratory research host. We believe this approach could also be useful for studyinginfections in different animal models of disease.