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Identification of pneumococcal colonization determinants in the stringent response pathway facilitated by genomic diversity

Overview of attention for article published in BMC Genomics, May 2015
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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 (80th percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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Title
Identification of pneumococcal colonization determinants in the stringent response pathway facilitated by genomic diversity
Published in
BMC Genomics, May 2015
DOI 10.1186/s12864-015-1573-6
Pubmed ID
Authors

Yuan Li, Nicholas J Croucher, Claudette M Thompson, Krzysztof Trzciński, William P Hanage, Marc Lipsitch

Abstract

Understanding genetic determinants of a microbial phenotype generally involves creating and comparing isogenic strains differing at the locus of interest, but the naturally existing genomic and phenotypic diversity of microbial populations has rarely been exploited. Here we report use of a diverse collection of 616 carriage isolates of Streptococcus pneumoniae and their genome sequences to help identify a novel determinant of pneumococcal colonization. A spontaneously arising laboratory variant (SpnYL101) of a capsule-switched TIGR4 strain (TIGR4:19F) showed reduced ability to establish mouse nasal colonization and lower resistance to non-opsonic neutrophil-mediated killing in vitro, a phenotype correlated with in vivo success. Whole genome sequencing revealed 5 single nucleotide polymorphisms (SNPs) affecting 4 genes in SpnYL101 relative to its ancestor. To evaluate the effect of variation in each gene, we performed an in silico screen of 616 previously published genome sequences to identify pairs of closely-related, serotype-matched isolates that differ at the gene of interest, and compared their resistance to neutrophil-killing. This method allowed rapid examination of multiple candidate genes and found phenotypic differences apparently associated with variation in SP_1645, a RelA/ SpoT homolog (RSH) involved in the stringent response. To establish causality, the alleles corresponding to SP_1645 were switched between the TIGR4:19F and SpnYL101. The wild-type SP_1645 conferred higher resistance to neutrophil-killing and competitiveness in mouse colonization. Using a similar strategy, variation in another RSH gene (TIGR4 locus tag SP_1097) was found to alter resistance to neutrophil-killing. These results indicate that analysis of naturally existing genomic diversity complements traditional genetics approaches to accelerate genotype-phenotype analysis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 32 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 10 31%
Student > Ph. D. Student 5 16%
Lecturer 2 6%
Student > Bachelor 2 6%
Professor > Associate Professor 2 6%
Other 4 13%
Unknown 7 22%
Readers by discipline Count As %
Agricultural and Biological Sciences 9 28%
Immunology and Microbiology 5 16%
Biochemistry, Genetics and Molecular Biology 4 13%
Medicine and Dentistry 4 13%
Computer Science 1 3%
Other 3 9%
Unknown 6 19%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 8. 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 14 October 2015.
All research outputs
#4,572,063
of 25,529,543 outputs
Outputs from BMC Genomics
#1,692
of 11,275 outputs
Outputs of similar age
#53,532
of 279,092 outputs
Outputs of similar age from BMC Genomics
#46
of 259 outputs
Altmetric has tracked 25,529,543 research outputs across all sources so far. Compared to these this one has done well and is in the 82nd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,275 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 84% 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 279,092 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 80% of its contemporaries.
We're also able to compare this research output to 259 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.