Genome-wide association study of signature genetic alterations among pseudomonas aeruginosa cystic fibrosis isolates

Wontae Hwang, Ji Hyun Yong, Kyung Bae Min, Kang-Mu Lee, Ben Pascoe, Samuel K Sheppard, Sang Sun Yoon

Research output: Contribution to journalArticlepeer-review

Abstract

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes diverse human infections including chronic airway infection in patients with cystic fibrosis (CF). Comparing the genomes of CF and non-CF PA isolates has great potential to identify the genetic basis of pathogenicity. To gain a deeper understanding of PA adaptation in CF airways, we performed a genome-wide association study (GWAS) on 1,001 PA genomes. Genetic variations identified among CF isolates were categorized into (i) alterations in protein-coding regions, either large- or small-scale, and (ii) polymorphic variation in intergenic regions. We introduced each CF-associated genetic alteration into the genome of PAO1, a prototype PA strain, and validated the outcomes experimentally. Loci readily mutated among CF isolates included genes encoding a probable sulfatase, a probable TonB-dependent receptor (PA2332~PA2336), L-cystine transporter (YecS, PA0313), and a probable transcriptional regulator (PA5438). A promoter region of a heme/hemoglobin uptake outer membrane receptor (PhuR, PA4710) was also different between the CF and non-CF isolate groups. Our analysis highlights ways in which the PA genome evolves to survive and persist within the context of chronic CF infection.
Original languageEnglish
Article numbere1009681
JournalPLoS Pathogens
Volume17
Issue number6
DOIs
Publication statusPublished - 23 Jun 2021

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