Ellison, L. | Search bioRxiv

bioRxiv2026

Spatial lung niches shape Pseudomonas aeruginosa persistence

Chronic Pseudomonas aeruginosa lung infection is a major cause of morbidity and mortality in people with pre-existing lung disease. Once established, infection is rarely eradicated and often persists despite prolonged antimicrobial therapy, but the underlying mechanisms remain poorly understood. To define how P. aeruginosa occupies and adapts to diseased lung tissue, we applied host-pathogen spatial transcriptomics to profile over 23 million lung cells from explanted and resected lungs from people with Cystic Fibrosis (CF) and chronic obstructive pulmonary disease (COPD), mapping bacterial niches and transcriptional states in situ. We found that P. aeruginosa adopted distinct niche-linked states across chronically infected human lung tissue. Bacterial burden was highest in airway lumens, but bacteria also occupied submucosal glands, parenchyma and, unexpectedly, blood vessel lumens in CF tissue. Within airway lumens, two coupled host-pathogen states emerged: an alginate-rich biofilm-like state linked to PI3-positive neutrophil inflammation and host chemical-sensing programmes; and a motile, quorum-sensing state with activated type 6 secretion linked to human ciliary stress, epithelial remodelling and proteolytic injury. Intravascular bacteria co-localised with neutrophils, fibrin and vascular-remodelling signatures, suggesting local breach of barrier integrity and subsequent immune containment. P. aeruginosa also displayed disease-specific cellular associations, with neutrophil-dominated interactions in CF and greater association with macrophages and dendritic cells in COPD. Together, these data reveal chronic P. aeruginosa infection as a spatially partitioned ecosystem in which anatomical microenvironments impose distinct bacterial lifestyles and host inflammatory states. This niche-resolved framework helps explain how persistent infection can diversify within a single lung and suggests that eradication therapies may need to target multiple anatomical and cellular niches to be effective.

immunology↗

bioRxiv2026

History-dependent ephaptic interactions in paired olfactory receptor neurons

Olfactory sensing begins with the transduction of odors into receptor currents on the dendrites of olfactory receptor neurons (ORNs). In insects and many other arthropods, ORNs are grouped stereotypically in hair-like sensilla on the surface of olfactory organs, enabling mutual inhibition through non-synaptic ephaptic interactions (NSIs). Given the electrical, and therefore virtually instantaneous, nature of NSIs, it has been hypothesized that they contribute to processing fast temporal elements of mixed odor plumes. Here, we present single sensillum recordings and computational modeling that characterize NSIs during short offset dual-odor stimulations in the olfactory sensilla of adult female Drosophila melanogaster. We find in the experiments that the magnitude of inhibition between co-housed ORNs cannot be predicted by their instantaneous activity (firing rate) alone. It is adaptation-dependent, with strong effects only occurring when the inhibited ORN is adapted. This limits the usefulness of NSIs for fast odor processing when ORNs lack time to adapt. We reproduced the observed phenomena in a computational model and use this model to explain how the adaptation-dependence of NSI-mediated inhibition arises from nonlinearities in neural responses. We conclude that NSIs are unlikely to support the encoding of fast temporal dynamics in mixed odor stimuli, instead contributing to slower peripheral processing, supporting roles such as novelty detection. More broadly, we demonstrate how the nonlinear interactions of fairly simple electrical components lead to non-intuitive results, offering insight into the longstanding debate around ephaptic interactions in other systems, such as the mammalian CNS.

neuroscience↗