From a genetic point of view, it has been shown that the genome of chronic strains is highly mutated, allowing the adaptation to the pulmonary environment 8. In addition, the formation of biofilms is a very common phenomenon in these infections as well as the development of a mucoid phenotype 7. These changes result in the appearance of highly resistant and partially or completely depigmented strains.
This evolution is associated with phenotypic and genotypic changes in Pa strains, evolving into a pattern of persistence or chronicity. The progression of Pa infection is characterized in three stages from initial to intermittent and chronic 5, 6, according to the different CF clinical situations.
As an example, airway infections with Pa are associated with higher rates of FEV1 decline in CF patients 4. Pulmonary infections due to one of the most feared micro-organism in this context, Pseudomonas aeruginosa ( Pa), are among the primary causes of morbidity and mortality in CF patients 2, 3. Many bacteria have been identified as pathogens of CF lungs. This mucus obstructs the airways leading to repetitive pneumonia and lung function decline. In Cystic Fibrosis (CF), the dysfunction of the CFTR channel is responsible for the generation of a viscous mucus in many organs 1. 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. 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). However, the production of HHQ was equivalent between strain types. Especially, five AQs were discriminant: HQC5, HQNOC7, HQNOC7:1, db-PQS C9 and HQNOC9:1. Multivariate analyses showed that first colonization strains could be differentiated from chronic colonization ones, by producing notably more Alkyl-Quinolones (AQs) derivatives. 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).
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. The operation returns an array of the resultObjectType object.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. This operation enables external applications to delete position lines of a staffing profile identified by position id in PPM Center. This operation deletes position lines of a staffing profile in PPM Center.
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