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

Serge Michalet,Carine Commun,Bruna Gioia,Anne Doléans-Jordheim,Van Thanh Nguyen Ngoc,Jean-Luc Wolfender,Kodjo Nouwade,Marie-Geneviève Dijoux-Franca,Pierre-Marie Allard

doi:10.1038/s41598-021-99467-7

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.

Highlights

In Cystic Fibrosis (CF), the dysfunction of the CFTR channel is responsible for the generation of a viscous mucus in many o rgans[1]
A standardized definition of chronic Pseudomonas aeruginosa (Pa) infection is of great importance within clinical care as it would allow a rapid grouping of patients during clinical trials, as well as relevant comparisons between studies and laboratories[10,11]
The objective of our study was to compare the metabolic profiles, and more the AQs production, of 44 Pa strains isolated from 34 CF patients at different stages of infection and cultivated in vitro, in order to identify discriminant metabolites that would be differentially produced according to Pseu‐ domonas phenotype

Summary

Introduction

In Cystic Fibrosis (CF), the dysfunction of the CFTR channel is responsible for the generation of a viscous mucus in many o rgans[1]. It would be interesting to be able to rapidly define and characterize the stage of colonisation / infection in order to better adapt the respiratory sampling and analysis, the therapeutic management of the patients and to develop strategies to counteract this implantation. In addition to this benefit, chronic infections represent commonly used indicators of CF disease p rogression[10,11]. A standardized definition of chronic Pa infection is of great importance within clinical care as it would allow a rapid grouping of patients during clinical trials, as well as relevant comparisons between studies and laboratories[10,11]

Objectives

Methods

Results

Conclusion