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

Détails

Ressource 1Télécharger: 30103826_BIB_913D33DD50B5.pdf (887.21 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_913D33DD50B5
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia.
Périodique
Genome medicine
Auteur⸱e⸱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
Statut éditorial
Publié
Date de publication
23/08/2018
Peer-reviewed
Oui
Volume
10
Numéro
1
Pages
65
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
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.
Mots-clé
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
Oui
Création de la notice
20/08/2018 14:40
Dernière modification de la notice
30/04/2021 6:12
Données d'usage