Single-cell biology of Salmonella in infected host tissues

Pathogen properties in infected host tissues are crucial for disease and control. Novel single-cell technologies reveal an astonishing diversity of pathogen cells with disparate molecular compositions, fates, and impact on overall disease progression. A current key challenge is to understand the relation between these various pathogen subsets and their respective host microenvironments. As a first step towards this goal, we have implemented 3D imaging methods for infected tissues at nm to cm scales. We use these methods to determine how host structures modulate Salmonella sensitivity to antimicrobial chemotherapy. Our results show strong host impact across a wide range of scales and identify a particular compartment in spleen that provides a niche for long-term Salmonella survival during treatment with potent fluoroquinolone or beta-lactam antibiotics. The increasingly detailed understanding of important physico-chemical parameters in the host paves the way for establishing suitable in vitro models for in-depth molecular analysis under relevant in vivo-like conditions.