Tracing T3SS effectors in vivo during Salmonella infection in the zebrafish model

ended

Type III secretion systems (T3SS) are sophisticated “molecular needles” that many pathogenic Gram-negative bacteria use to establish infection. Salmonella enterica encodes two T3SS that are able to translocate a number of proteins, called effectors, from bacteria to the cytosol of the infected eukaryotic cell. These proteins manipulate host signal transduction pathways and cellular processes to the pathogen’s advantage. During the last two decades, many studies have importantly contributed to the identification and characterization of many of these effectors. However, the subcellular localization, host target and biological role of an important number of them remain unknown. The majority of findings of T3SS effectors come from studies using surrogate in vitro models, like epithelial cells or macrophages. In these cases, the extrapolation of results to an in vivo scenario is not always possible. On the other hand, important mammalian models to study Salmonella infection, like mice, do not allow tracking the pathogen once inside its host. Here, we propose an innovative approach using the zebrafish (Danio rerio) as a relevant vertebrate model to dissect the biological role of Salmonella T3SS effectors during host infection. Zebrafish embryo model allow for rapid, non-invasive and real-time analysis of bacterial infections. We will take advantage of the small size and optical transparency of larval zebrafish for live-cell imaging of host-pathogen interaction experiments. This approach allows real-time cell-resolution monitoring of T3SS effectors. This will significantly improve our understanding of infectious diseases in an relevant in vivo context. This project not only will stablish a new in vivo model in the hosting laboratory and open new posibilities in the study of T3SS effectors, but also it will contribute to strengthen my previous experience boosting my future scientific career.