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Identification of the minimal cytolytic unit for streptolysin S and an expansion of the toxin family

Overview of attention for article published in BMC Microbiology, July 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#43 of 1,146)
  • High Attention Score compared to outputs of the same age (88th percentile)
  • High Attention Score compared to outputs of the same age and source (97th percentile)

Mentioned by

blogs
2 blogs
twitter
1 tweeter

Citations

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5 Dimensions

Readers on

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21 Mendeley
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Title
Identification of the minimal cytolytic unit for streptolysin S and an expansion of the toxin family
Published in
BMC Microbiology, July 2015
DOI 10.1186/s12866-015-0464-y
Pubmed ID
Authors

Evelyn M. Molloy, Sherwood R. Casjens, Courtney L. Cox, Tucker Maxson, Nicole A. Ethridge, Gabriele Margos, Volker Fingerle, Douglas A. Mitchell

Abstract

Streptolysin S (SLS) is a cytolytic virulence factor produced by the human pathogen Streptococcus pyogenes and other Streptococcus species. Related "SLS-like" toxins have been characterized in select strains of Clostridium and Listeria, with homologous clusters bioinformatically identified in a variety of other species. SLS is a member of the thiazole/oxazole-modified microcin (TOMM) family of natural products. The structure of SLS has yet to be deciphered and many questions remain regarding its structure-activity relationships. In this work, we assessed the hemolytic activity of a series of C-terminally truncated SLS peptides expressed in SLS-deficient S. pyogenes. Our data indicate that while the N-terminal poly-heterocyclizable (NPH) region of SLS substantially contributes to its bioactivity, the variable C-terminal region of the toxin is largely dispensable. Through genome mining we identified additional SLS-like clusters in diverse Firmicutes, Spirochaetes and Actinobacteria. Among the Spirochaete clusters, naturally truncated SLS-like precursors were found in the genomes of three Lyme disease-causing Borrelia burgdorferi sensu lato (Bbsl) strains. Although unable to restore hemolysis in SLS-deficient S. pyogenes, a Bbsl SLS-like precursor peptide was converted to a cytolysin using purified SLS biosynthetic enzymes. A PCR-based screen demonstrated that SLS-like clusters are substantially more prevalent in Bbsl than inferred from publicly available genome sequences. The mutagenesis data described herein indicate that the minimal cytolytic unit of SLS encompasses the NPH region of the core peptide. Interestingly, this region is found in all characterized TOMM cytolysins, as well as the novel putative TOMM cytolysins we discovered. We propose that this conserved region represents the defining feature of the SLS-like TOMM family. We demonstrate the cytolytic potential of a Bbsl SLS-like precursor peptide, which has a core region of similar length to the SLS minimal cytolytic unit, when modified with purified SLS biosynthetic enzymes. As such, we speculate that some Borrelia have the potential to produce a TOMM cytolysin, although the biological significance of this finding remains to be determined. In addition to providing new insight into the structure-activity relationships of SLS, this study greatly expands the cytolysin group of TOMMs.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 19%
Other 3 14%
Student > Master 3 14%
Unspecified 2 10%
Student > Bachelor 2 10%
Other 7 33%
Readers by discipline Count As %
Chemistry 5 24%
Agricultural and Biological Sciences 5 24%
Biochemistry, Genetics and Molecular Biology 4 19%
Unspecified 3 14%
Philosophy 1 5%
Other 3 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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 07 September 2015.
All research outputs
#440,487
of 6,305,233 outputs
Outputs from BMC Microbiology
#43
of 1,146 outputs
Outputs of similar age
#22,415
of 193,678 outputs
Outputs of similar age from BMC Microbiology
#1
of 43 outputs
Altmetric has tracked 6,305,233 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 93rd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,146 research outputs from this source. They receive a mean Attention Score of 2.9. This one has done particularly well, scoring higher than 96% 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 193,678 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 43 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 97% of its contemporaries.