It has been reported that Mycobacterium tuberculosis forms biofilm-like architectures, termed ‘cords’, that have been implicated in pathogenesis. So far, cord formation, biogeography within these structures and their functions during infection are not well understood. Thacker and colleagues showed in a mouse lung-on-chip model as well as in a mouse model that intracellular cord formation is an important feature of early pathogenesis in the alveolar microenvironment. They reported an attenuated inflammatory response in infected cells with cord architectures. This effect was mediated by compression of host cell nuclei via mechanical forces exerted by intracellular M. tuberculosis, which resulted in reduced activity of the histone deacetylase HDAC1. Moreover, cord growth enabled the dissemination of the bacteria between tight junctions of epithelial cells to new tissue niches. Next, the authors showed that compression of the lipids in the outer leaflet of the mycomembrane enabled the tight packing and long-range order of the cords, which promoted their mechanical rigidity. Moreover, cording architectures were shown to reduce the potency of antibiotic treatment, which the authors speculate could in part be due to reduced antibiotic penetration. In sum, the data presented in this study increase our understanding of these microbial non-surface-attached, tightly self-adhering structures and their functional roles during infection.