Alkyl-Quinolones derivatives as potential biomarkers for Pseudomonas aeruginosa infection chronicity in Cystic Fibrosis

Abstract

In Cystic Fibrosis (CF), a rapid and standardized definition of chronic infection would allow a better management of Pseudomonas aeruginosa (Pa) infections, as well as a quick grouping of patients during clinical trials allowing better comparisons between studies. With this purpose, we compared the metabolic profiles of 44 in vitro cultures of Pa strains isolated from CF patients at different stages of infection in order to identify metabolites differentially synthetized according to these clinical stages. Compounds produced and secreted by each strain in the supernatant of a liquid culture were analysed by metabolomic approaches (UHPLC-DAD-ESI/QTOF, UV and UPLC-Orbitrap, MS). Multivariate analyses showed that first colonization strains could be differentiated from chronic colonization ones, by producing notably more Alkyl-Quinolones (AQs) derivatives. Especially, five AQs were discriminant: HQC5, HQNOC7, HQNOC7:1, db-PQS C9 and HQNOC9:1. However, the production of HHQ was equivalent between strain types. The HHQ/HQNOC9:1 ratio was then found to be significantly different between chronic and primo-colonising strains by using both UV (p = 0.003) and HRMS data (p = 1.5 × 10–5). Our study suggests that some AQ derivatives can be used as biomarkers for an improved management of CF patients as well as a better definition of the clinical stages of Pa infection.

A year in review: Real world evidence, functional monitoring and emerging therapeutics in 2021

“…The functional response of the community dictates response to therapy, affects clinical outcomes and provides potential novel therapeutic targets and potential novel biomarkers [96] . For example, specific virulence factors produced by P. aeruginosa , the alkyl quinolones, are promising biomarkers for pulmonary P. aeruginosa and are also potential therapeutic targets [97] , [98] , [99] . As more studies confirm that P. aeruginosa persists in airways of ‘eradicated’ patients, we anticipate that focus may switch from attempting to eradicate infection , towards manipulating the functional response of the microbiome [100] .…”