Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_913D33DD50B5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia.
Journal
Genome medicine
Author(s)
Giulieri S.G., Baines S.L., Guerillot R., Seemann T., Gonçalves da Silva A., Schultz M., Massey R.C., Holmes N.E., Stinear T.P., Howden B.P.
ISSN
1756-994X (Electronic)
ISSN-L
1756-994X
Publication state
Published
Issued date
23/08/2018
Peer-reviewed
Oui
Volume
10
Number
1
Pages
65
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Large-scale genomic studies of within-host diversity in Staphylococcus aureus bacteraemia (SAB) are needed to understanding bacterial adaptation underlying persistence and thus refining the role of genomics in management of SAB. However, available comparative genomic studies of sequential SAB isolates have tended to focus on selected cases of unusually prolonged bacteraemia, where secondary antimicrobial resistance has developed.
To understand bacterial genetic diversity during SAB more broadly, we applied whole genome sequencing to a large collection of sequential isolates obtained from patients with persistent or relapsing bacteraemia. After excluding genetically unrelated isolates, we performed an in-depth genomic analysis of point mutations and chromosome structural variants arising within individual SAB episodes.
We show that, while adaptation pathways are heterogenous and episode-specific, isolates from persistent bacteraemia have a distinctive molecular signature, characterised by a low mutation frequency and high proportion of non-silent mutations. Analysis of structural genomic variants revealed that these often overlooked genetic events are commonly acquired during SAB. We discovered that IS256 insertion may represent the most effective driver of within-host microevolution in selected lineages, with up to three new insertion events per isolate even in the absence of other mutations. Genetic mechanisms resulting in significant phenotypic changes, such as increases in vancomycin resistance, development of small colony phenotypes, and decreases in cytotoxicity, included mutations in key genes (rpoB, stp, agrA) and an IS256 insertion upstream of the walKR operon.
This study provides for the first time a large-scale analysis of within-host genomic changes during invasive S. aureus infection and describes specific patterns of adaptation that will be informative for both understanding S. aureus pathoadaptation and utilising genomics for management of complicated S. aureus infections.
Keywords
Bacteremia/microbiology, Genes, Bacterial, Point Mutation, Polymorphism, Genetic, Staphylococcus aureus/genetics, Staphylococcus aureus/isolation & purification, Staphylococcus aureus/pathogenicity, Bacteraemia, Genomics, Persistence, Staphylococcus aureus, Within-host diversity
Pubmed
Web of science
Open Access
Yes
Create date
20/08/2018 14:40
Last modification date
30/04/2021 6:12
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