Please use this identifier to cite or link to this item:
Email to ask for this document in a different format
Title: Transcriptomic analysis of longitudinal Burkholderia pseudomallei infecting the cystic fibrosis lung.
Authors: Price, Erin P
Viberg, Linda T
Kidd, Timothy J
Bell, Scott C
Currie, Bart J
Sarovich, Derek S
Citation: Microbial genomics 2018-08; 4(8)
Abstract: The melioidosis bacterium, Burkholderia pseudomallei, is increasingly being recognised as a pathogen in patients with cystic fibrosis (CF). We have recently catalogued genome-wide variation of paired, isogenic B. pseudomallei isolates from seven Australasian CF cases, which were collected between 4 and 55 months apart. Here, we extend this investigation by documenting the transcriptomic changes in B. pseudomallei in five cases. Following growth in an artificial CF sputum medium, four of the five paired isolates exhibited significant differential gene expression (DE) that affected between 32 and 792 genes. The greatest number of DE events was observed between the strains from patient CF9, consistent with the hypermutator status of the latter strain, which is deficient in the DNA mismatch repair protein MutS. Two patient isolates harboured duplications that concomitantly increased expression of the β-lactamase-encoding gene penA, and a 35 kb deletion in another abolished expression of 29 genes. Convergent expression profiles in the chronically-adapted isolates identified two significantly downregulated and 17 significantly upregulated loci, including the resistance-nodulation-division (RND) efflux pump BpeEF-OprC, the quorum-sensing hhqABCDE operon, and a cyanide- and pyocyanin-insensitive cytochrome bd quinol oxidase. These convergent pathoadaptations lead to increased expression of pathways that may suppress competing bacterial and fungal pathogens, and that enhance survival in oxygen-restricted environments, the latter of which may render conventional antibiotics less effective in vivo. Treating chronically adapted B. pseudomallei infections with antibiotics designed to target anaerobic infections, such as the nitroimidazole class of antibiotics, may significantly improve pathogen eradication attempts by exploiting this Achilles heel.
Click to open PubMed article:
Click to open Pubmed Article:
Journal title: Microbial genomics
Publication Date: 2018-08
Type: Journal Article
DOI: 10.1099/mgen.0.000194
Appears in Collections:(a) NT Health Research Collection

Files in This Item:
There are no files associated with this item.

Items in ePublications are protected by copyright, with all rights reserved, unless otherwise indicated.