Steve Diggle (@digglelab.bsky.social)

Whole-tissue imaging reveals intrastrain diversity shapes the spatial organization of Pseudomonas aeruginosa in a murine infection model | mSphere Intrastrain genetic and phenotypic diversity within Pseudomonas aeruginosa populations is common in chronic pulmonary infections. While this intrastrain heterogeneity is a hallmark of chronic infection, its consequences for the spatial organization of P. aeruginosa within the airways remain unclear. Here, we demonstrate that the loss of O-specific antigen in a subpopulation of P. aeruginosa significantly alters the spatial architecture of P. aeruginosa, without changing the total population size or composition. Using a combination of tissue clearing and hybridization chain reaction RNA-FISH in a murine lung infection model, we mapped the localization of genetically distinct P. aeruginosa variants in mixed populations in vivo. These findings reveal that genetic diversification within a strain can reshape the infection landscape at the micron scale, highlighting the overlooked role of intrastrain dynamics in shaping the microbiogeography of infections and influencing host-pathogen interactions. https://journals.asm.org/doi/10.1128/msphere.00657-25