Single-cell transcriptomics is revolutionizing our understanding of host-pathogen interactions by providing a cellular-level overview of infection trajectories. However, because cells needs to be dissociated, the technology falls short in providing in vivo spatial information crucial for tissue analysis. Furthermore, while some commercial solutions are emerging, they cannot provide the sufficient resolution to detect and localize pathogens accurately. To overcome these limitations, we are establishing a novel methodology combining near-single-cell resolution spatial transcriptomic approach with pathogen-targeting probes. We will validated through fluorescence microscopy and H&E staining, offering visual confirmation of bacterial presence in intestinal tissues. This integrated approach enables the simultaneous profiling of host-transcriptomes and precise spatial mapping of bacterial activity, facilitating a more comprehensive understanding of host-pathogen interactions during infection.