P20

The rise of multidrug-resistant tuberculosis and the dearth of new antibiotic development place an existential strain on successful therapy. Breakthrough strategies that go beyond classical antibiotic mechanisms are needed to combat this looming public health crisis. Reconceptualizing antibiotic therapy in the richer context of host-pathogen interaction is required for innovative solutions. Most studies using patient’s material are based on sputum and blood samples which do not reflect the pathological mechanisms occurring in the lung. We assembled a cohort of tuberculosis patients (MDR, XDR, susceptible) who received lung surgery after initial anti-microbial therapy. We analyze spatially resolved transcriptomes of the resected material and generated tissue microarrays of characteristic regions e.g., late and early granuloma, tertiary lymphoid structures, multinucleated cell, T cell, and macrophage areas, diffuse inflammation, and non-affected tissue for multispectral imaging. Spatial transcriptomics and tissue microarrays include lung material of patients from different strata e.g., gender, age, comorbidities, MDR/XDR or susceptible tuberculosis, treatment regimen and duration, etc. Results will provide us with signatures within morphological areas that are linked to a beneficial disease outcome and recapitulate the immunological and metabolomic processes differentiating the patient strata. This may constitute a promising target for supportive host-directed therapies.