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

doi:10.1371/journal.ppat.1009681

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

PLoS Pathog. 2021 Jun 23;17(6):e1009681. doi: 10.1371/journal.ppat.1009681. eCollection 2021 Jun.

Authors

Wontae Hwang^{1

2}, Ji Hyun Yong^{1

2}, Kyung Bae Min^{1

2}, Kang-Mu Lee^{1

2}, Ben Pascoe³, Samuel K Sheppard³, Sang Sun Yoon^{1

2

4

5}

Affiliations

¹ Department of Microbiology and Immunology, Seoul, Republic of Korea.
² Brain Korea 21 PLUS Project for Medical Sciences, Seoul, Republic of Korea.
³ The Milner Centre for Evolution, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath, United Kingdom.
⁴ Institute for Immunology and Immunological Diseases, Seoul, Republic of Korea.
⁵ Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cystic Fibrosis / microbiology*
Genetic Variation
Genome-Wide Association Study
Humans
Pseudomonas Infections / genetics*
Pseudomonas aeruginosa / genetics*

Grants and funding

This work was supported by grants received by S.S.Y. from the National Research Foundation (NRF) of Korea, which is funded by the Korean Government (2017M3A9F3041233 and 2019R1A6A1A03032869). This research was also supported by a grant received by S.S.Y. from the Korean Health Technology R&D Project through the Korean Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1324). All funders listed had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.