The introduction of Trikafta has brought significant clinical benefits to individuals with cystic fibrosis (CF) eligible for treatment. However, the variations observed in treatment response suggest the existence of mechanisms independent of those directly related to CFTR. Understanding whether among these mechanisms there is also a direct or indirect effect on Pseudomonas aeruginosa would provide further insights into how Trikafta acts and its impact on bacterial functions that could influence the effectiveness of therapy.
In this study, P. aeruginosa strains (types) were isolated from 12 individuals with CF just before the initiation of Trikafta treatment, and after 12 and 18 months of treatment. Additionally, clinical data such as respiratory function were collected.
The strains were tested for antibiotic susceptibility and characterized for various bacterial phenotypes (e.g., secretion of harmful factors like pyocyanin). The effect of these strains on bronchial epithelial cells with normal CFTR or the F508del mutation was then evaluated to understand whether treatment with Trikafta influences the inflammatory activity of P. aeruginosa. Additionally, the genetic material (both DNA and RNA) of longitudinal clonal strains was sequenced to assess whether Trikafta induces mutations and/or alters bacterial virulence. Finally, the obtained data were correlated with the clinical response.
It has been observed that pyocyanin levels correlate with respiratory function. Person-specific differences in antibiotic susceptibility, impact on the inflammatory response, and biofilm (a bacterial aggregation form) production associated with Trikafta treatment have been observed. Furthermore, initial evidence suggests that Trikafta induces mutations that may alter bacterial virulence.
The analysis will be now extended to other individuals with CF over time to understand how Trikafta modifies P. aeruginosa in the long term. Identifying specific bacterial traits as risk factors for the effectiveness of Trikafta would lead to careful monitoring and the use of targeted antibiotic therapies.