Cryo-electron tomography (cryo-ET) has revolutionized visualization of bacterial nanomachines by revealing molecular structures in situ under near-native conditions. This review highlights recent advances extending cryo-ET from isolated cells to host-microbe interactions within intact tissues. We discuss technical solutions for large-volume imaging such as cryo-focused ion beam milling, correlative light and electron microscopy, and serial lift-out workflows that preserve native structural context. Computational developments in AI-driven denoising, segmentation, and sub-tomogram averaging enhance interpretability of low-dose tomograms. Using examples from predatory bacteria, intracellular pathogens, and squid symbionts, we demonstrate how cryo-ET elucidates mechanistic details of microbial interactions.
Leemburg et al. (Thu,) studied this question.