Genomic and transcriptomic characterization of Pseudomonas aeruginosa small colony variants derived from a chronic infection model

Irvine, S., Bunk, B., Bayes, H. K., Spröer, C., Connolly, J. P.R., Six, A., Evans, T. J. , Roe, A. J. , Overmann, J. and Walker, D. (2019) Genomic and transcriptomic characterization of Pseudomonas aeruginosa small colony variants derived from a chronic infection model. Microbial Genomics, 5(4), (doi:10.1099/mgen.0.000262) (PMID:30920365) (PMCID:PMC6521587)

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Abstract

Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis, well-characterized phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoid P. aeruginosa strain NH57388A. Using a combination of single-molecule real-time (PacBio) and Illumina sequencing we identify a large genomic inversion in the SCV through recombination between homologous regions of two rRNA operons and an associated truncation of one of the 16S rRNA genes and suggest this may be the genetic switch for conversion to the SCV phenotype. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance because the appearance of SCVs during chronic infection is associated with declining lung function.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walker, Professor Daniel and Roe, Professor Andrew and Evans, Professor Tom and Six, Dr Anne and Connolly, Dr James and Irvine, Dr Sharon and Bayes, Dr Hannah
Authors: Irvine, S., Bunk, B., Bayes, H. K., Spröer, C., Connolly, J. P.R., Six, A., Evans, T. J., Roe, A. J., Overmann, J., and Walker, D.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Microbial Genomics
Publisher:Microbiology Society
ISSN:2057-5858
ISSN (Online):2057-5858
Published Online:28 March 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Microbial Genomics 2019
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
530731Scottish Clinical Pharmacology and Pathology Programme (SCP3)Iain McInnesMedical Research Council (MRC)G1000419III -IMMUNOLOGY
724641Protein Antibiotics: Discovery, mode of action and developmentDaniel WalkerWellcome Trust (WELLCOTR)201505/Z/16/ZIII - BACTERIOLOGY