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

Overview of attention for article published in Genome Medicine, August 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (88th percentile)

Mentioned by

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34 tweeters

Citations

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16 Dimensions

Readers on

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47 Mendeley
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Title
Genomic exploration of sequential clinical isolates reveals a distinctive molecular signature of persistent Staphylococcus aureus bacteraemia
Published in
Genome Medicine, August 2018
DOI 10.1186/s13073-018-0574-x
Pubmed ID
Authors

Stefano G. Giulieri, Sarah L. Baines, Romain Guerillot, Torsten Seemann, Anders Gonçalves da Silva, Mark Schultz, Ruth C. Massey, Natasha E. Holmes, Timothy P. Stinear, Benjamin P. Howden

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.

Twitter Demographics

The data shown below were collected from the profiles of 34 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 47 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 47 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 26%
Student > Ph. D. Student 8 17%
Student > Doctoral Student 5 11%
Professor > Associate Professor 4 9%
Student > Bachelor 4 9%
Other 8 17%
Unknown 6 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 11 23%
Biochemistry, Genetics and Molecular Biology 11 23%
Immunology and Microbiology 8 17%
Medicine and Dentistry 7 15%
Environmental Science 2 4%
Other 1 2%
Unknown 7 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 19. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 November 2018.
All research outputs
#1,232,600
of 17,370,809 outputs
Outputs from Genome Medicine
#278
of 1,156 outputs
Outputs of similar age
#33,079
of 284,354 outputs
Outputs of similar age from Genome Medicine
#1
of 1 outputs
Altmetric has tracked 17,370,809 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,156 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 23.4. This one has done well, scoring higher than 75% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 284,354 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 88% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them