Spatial lung niches shape Pseudomonas aeruginosa persistence

07 Jul 20264 min read0 viewsVerified Feed

GIST (Key Takeaways)

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+ 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.