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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.
![A workflow for evaluating defense mechanisms in an evolutionary context: Starting from an initial discovery of a defense mechanism [typically bioinformatic (2) or experimental (3)], we emphasize the importance of explicitly identifying alternative defense and nondefense evolutionary hypotheses (1) and using these hypotheses to drive additional experimental and bioinformatic tests. Arrows highlight iterative integration (4): bioinformatic discoveries (2) can drive experimental predictions (3) by inspiring new testable hypotheses (1). Similarly, experimental data (3) can drive bioinformatic predictions (2), a process mediated by new functional hypotheses (1). Mechanisms can cycle through these steps multiple times as new data accumulate, both within and across multiple studies (4).](https://cdn.bsky.app/img/feed_thumbnail/plain/did:plc:w6ipl5c32bene36ros2fqv3m/bafkreicua5c5bzjws7kmxqdewuqghobz3czcmpv43um5qym3tozo44n5re)
