Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infections

Meirelles, L. A.; Vayena, E.; Debache, A.; Schmidt, E.; Rossy, T.; Distler, T.; Hatzimanikatis, V.; Persat, A.

doi:10.1101/2024.09.09.611974

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bioRxiv · 10.1101/2024.09.09.611974

Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infections

Meirelles, L. A.·Vayena, E.·Debache, A.·Schmidt, E.·Rossy, T.·Distler, T.·Hatzimanikatis, V.·Persat, A.

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Abstract

Pseudomonas aeruginosa causes antibiotic-resilient acute and chronic pneumonia, but the mechanisms by which it adapts to the airway environment are poorly understood. Here, we investigated P. aeruginosa pathoadaptive mechanisms in tissue-engineered human airway organoids. Using transposon sequencing in situ, we decoded how P. aeruginosa survives on the mucosal surface during antibiotic treatment. Biofilm formation emerged as a major driver of P. aeruginosa colonization. Mutants that extensively produce biofilms on mucus show limited exploratory behavior, which limits nutrient access, slowing down their growth. Conversely, biofilm-dwelling P. aeruginosa better tolerate antibiotics via biophysical mechanisms. Finally, biofilms can shelter less-tolerant but more cytotoxic strains, thereby contributing to genotypic heterogeneity. P. aeruginosa must therefore adapt to conflicting physical and biological selective pressures to initiate chronic infections.

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Meirelles, L. A., Vayena, E., Debache, A., Schmidt, E., Rossy, T., Distler, T., Hatzimanikatis, V., Persat, A.. 2024-09-09. Pseudomonas aeruginosa faces a fitness trade-off between mucosal colonization and antibiotic tolerance during airway infections. https://doi.org/10.1101/2024.09.09.611974

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