Genomic characterization of Pseudomonas aeruginosa adaptation mechanisms in bronchiectasis patients

铜绿假单胞菌在支气管扩张患者体内的适应机制的基因组特征分析

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Abstract

OBJECTIVES: Pseudomonas aeruginosa is one of the main causes of chronic bronchial infection (CBI), especially in patients with chronic underlying diseases such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), asthma and bronchiectasis (BQ). Compared to P. aeruginosa CBI in CF, BQ infection has historically received less attention. The aim of this study was to determine the antibiotic susceptibility profile of 100 isolates recovered from 100 patients with P. aeruginosa CBI BQ and to characterize some of the adaptation mechanisms in 55 isolates by whole genome sequencing (WGS). METHODS: Susceptibility testing to 10 antipseudomonal agents was done by MicroScan WalkAway broth microdilution system. WGS was performed using the Illumina DNA Prep library preparation kit. Indexed libraries were sequenced on an Illumina MiSeq benchtop sequencer (300 base pairs paired-end reads). RESULTS: The most common loss-of-function mutations occurred in genes encoding the MexAB-OprM efflux-pump system, the pvd cluster and the fpvA receptor, and genes involved in twitching motility such as chpA and fimV. CONCLUSIONS: Our data indicates that P. aeruginosa adapts by accumulating loss-of-function mutations in several genes, resulting in changes to different phenotypes that may guide the development of new alternative treatment therapies.

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