We discovered that host cells can prevent the actin-based motility of Shigella by compartmentalizing bacteria inside septin cages for targeting to autophagy. From this we hypothesized that understanding the role of septins, an enigmatic component of the cytoskeleton, will provide insights into bacterial infection and cellular immunity. We recently pioneered a ‘bottom up’ cellular microbiology approach to study cellular immunity and discovered a fundamental link between bacterial cell biology and the assembly of septin cages around Shigella. A major issue is now to fully decipher the underlying molecular and cellular events, and to validate these events analyzed in vitro during bacterial infection in vivo using relevant animal models. We developed zebrafish as an important model to study the cell biology of infection and therapeutic potential of targeting the cytoskeleton in vivo. Our findings should be of interest for both cell and infection biologists, and provide cutting edge platforms for studies at the single cell and whole animal level.