Backgrounds The respiratory pathogen nontypeable Haemophilus influenzae (NTHi) is encountered in a significant proportion in the lower airways of Chronic Obstructive Pulmonary Disease (COPD) patients. The COPD lung is likely to be a unique niche favouring its adaptation to persistent infection. Objectives To unravel NTHi evolutionary dynamics in the lung of the COPD patient over time, and to identify microbial patho-adaptive features. Methods Ninety-two NTHi isolates from sputum samples of 13 COPD patients at exacerbation, recovered in a prospective longitudinal study (2000-2014), were genome sequenced: (a) Pacific Biosciences longread sequencing was used to generate complete assemblies for one representative of each clonal type; (b) Illumina short-read sequencing was applied to all isolates. Genome assembly used a customized pipeline and raw reads were also aligned to the PacBio reference genomes to generate variant tables for each set of clonal type isolates. Functional characterization of parallel evolutionrelated allelic variation was analyzed for selected genes. Conclusions Ninety-two NTHi COPD isolates have been (i) phylogenomically analyzed in the context of all publicly available NTHi genome sequences, (ii) organized in 33 clonal types, (iii) used to establish variation in NTHi genome architecture, (iv) used to identify traits of parallel evolution by fixing at least one single nucleotide variant in more than one clonal type. Detailed analysis of the fadL-ompP1 gene parallel evolution and allelic variation will be discussed, in terms of its role as an exogenous long-chain fatty acids transporter, as a ligand of the human receptor CEACAM-1 and as a source of antigenic variation.

Trabajo presentado en el 7th Congress of European Microbiologists (FEMS2017), celebrado en Valencia (España), del 9 al 13 de julio de 2017

Peer reviewed