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- W4379979908 abstract "Objectives: The CF airway is associated with lower surface pH and relative hypoxia within sputum plugs. The impact of CFTR modulators on pH and O2 state is unknown. Restoration of chloride/bicarbonate transport, airway surface hydration and mucociliary clearance suggests a normalisation of airway pH and O2 levels. We investigated the effect of pH and O2 state on tobramycin sensitivity and virulence/persistence phenotypes of CF clinical isolates of Pseudomonas aeruginosa (Pa) in vitro, to help predict the impact of modulators on CF airway infection. Methods: 11 CF Pa isolates and type strain, PA14, were inoculated in 10 ml aliquots of acidic pH 6.5, and neutral pH 7.4 Muller Hinton Broth 2, sealed with breathable membranes and incubated at 37°C overnight in normal (21%) or low (6%) O2 environments. Bacteria were serial passaged under the same conditions for 2 more days. Outcome measures were MIC to tobramycin, mucoidy (congo red agar) and pyoverdine production (relative fluorescent intensity). Results: Acidic pH was associated with significantly higher MICs to tobramycin, in normal and low O2 environments (p = 0.0234 and p = 0.0156, respectively). MICs were not O2 dependent at either pH. pH had no clear impact on mucoidy (subjectively scored); impact of O2 was strain specific, with 6/12 isolates showing increased mucoidy in low O2 in at least one pH condition, while 1 decreased. When data were pooled across pHs to compare impact of O2 state, pyoverdine was significantly higher in normoxic cultures (p < 0.0001). Conclusions: CF airway has low pH and areas of relative hypoxia. Assuming restoration of CFTR function will partially restore normality, our data suggests that sensitivity to tobramycin may increase (a given concentration of antibiotic being more effective) and isolates may demonstrate less mucoidy, a phenotype associated with chronic persistence. Work on an increased number of isolates is ongoing." @default.
- W4379979908 created "2023-06-10" @default.
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- W4379979908 date "2023-06-01" @default.
- W4379979908 modified "2023-09-27" @default.
- W4379979908 title "EPS9.01 An in vitro model to predict the impact of CFTR functional restoration in the cystic fibrosis airway on Pseudomonas aeruginosa anti-microbial resistance, persistence and virulence" @default.
- W4379979908 doi "https://doi.org/10.1016/s1569-1993(23)00367-3" @default.
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