Infection-dependent antibiotic response phenotypes emerge during chronic airway adaptation of Pseudomonas aeruginosa

In cystic fibrosis longitudinal isolates of Pseudomonas aeruginosa, antibiotic response phenotypes in an airway epithelial ALI model only partly match conventional susceptibility testing, with discordant survival linked to chronic persistence.

• Why it matters: Standard susceptibility testing captures resistance emergence but may miss infection-environment adaptations that reshape how chronic airway isolates respond to antibiotics.
• What they did: Six longitudinal isolate pairs were tested for growth changes after tobramycin, ceftazidime, and ciprofloxacin under standard lab conditions and compared with bacterial burden changes after treatment in differentiated airway epithelial ALI cultures, using confocal microscopy and whole-genome sequencing context.
• The result: Major resistance phenotypes were largely reproduced in ALI, but concordance differed by antibiotic; isolates deemed susceptible in standard tests showed substantial ALI survival, especially those recovered after prolonged persistence, with genomic mutations reflecting both resistance and chronic adaptation.

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