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Predicting resistance from whole genome analysis

Impact of lung transplantation on the phylogenetic diversity of Pseudomonas aeruginosa isolates from end-stage cystic fibrosis patients

April 18 • O0236

R. Datar1, A. Coello Pelegrin1, S. Orenga1, A. Perry2, J. Samuel2, A. van Belkum1, H. Goossens3, V. Chalansonnet1

1) R&D Microbiology, bioMérieux, La Balme-les-Grottes, France
2) Microbiology Department, Freeman Hospital, Newcastle upon Tyne, NE7 7DN, UK
3) Laboratory of Medical Microbiology, Vaccine and Infectious Diseases Institute, University of Antwerp, Antwerp, Belgium

Background: Impaired lung function and chronic infections due to colonization and infection by complex microbiota elevates the health risk of patients with cystic fibrosis (CF) which can ultimately lead to full respiratory insufficiency and death. For patients with end-stage CF lung disease, lung transplantation (LTx) is the only remaining therapeutic option. In this context, Pseudomonas aeruginosa is a principal cause of chronic lung infections and such strains display different phenotypic and genomic characteristics compared to their wild-type ancestors.
The aim of this study was to analyze the epidemiology and evolution of P. aeruginosa strains serially obtained from CF patients, and a non-CF bronchiectasis patient, who underwent LTx (Newcastle upon Tyne, UK).

Materials/methods: A panel of 708 P. aeruginosa strains from different niches and 4 different strain collections were analyzed for genomic relatedness. These comprised the bioMérieux collection (n = 219), Kos collection (n = 390), Pirnay collection (n = 63) and sequential strains from six LTx patients (n = 36). For each LTx patient, samples were collected before, during and after the LTx at different time points. Multi-locus sequence typing (MLST) and construction of a core genome based phylogenetic tree using bioinformatics tools was employed to define the genomic relatedness among the different P. aeruginosa strains.

Results: The genome wide assessment showed clustering with respect to the origin of the isolates i.e from patients from whom they were isolated implying intra-individual variability. The MLST profiles showed the P. aeruginosa strains from the Newcastle CF patients, but not the bronchiectasis one, had previously unidentified sequence types. Strains from Newcastle were scattered among the phylogenetic tree, indicating that the patients were neither cross-colonized nor cross-infected.

Conclusions: P. aeruginosa isolates from CF patients disclose very specific traits, but they could be phylogenetically distant between patients. On the other hand, LTx and associated treatment had no impact on the phylogenetic type of the P. aeruginosa strain harbored by each studied patient. Studying the presence of SNPs may aid our understanding of elevated resistance to the drugs used for treatment.


Genome analysis

2-Hour Oral session