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

BMC Microbiology

Research Article

Volker Fingerle¹  Gabriele Margos¹  Evelyn M. Molloy²  Courtney L. Cox³  Douglas A. Mitchell⁴  Tucker Maxson⁵  Sherwood R. Casjens⁶  Nicole A. Ethridge⁷ 

[1] Bavarian Health and Food Safety Authority, National Reference Centre for Borrelia, Oberschleissheim, Germany;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Department of Microbiology, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Department of Microbiology, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Department of Chemistry, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Department of Chemistry, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;Division of Microbiology and Immunology, Department of Pathology, University of Utah Medical School, 84112, Salt Lake City, UT, USA;School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, 61801, Urbana, IL, USA;

关键词: Streptolysin S;    Streptococcus pyogenes;    Streptococcus;    Thiazole/oxazole-modified microcin;    Cytolysin;    Borrelia burgdorferi;    Lyme disease;    Linear azole-containing peptide;   

DOI  :  10.1186/s12866-015-0464-y

 received in 2015-01-02, accepted in 2015-06-11,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundStreptolysin 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.ResultsIn 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Molloy et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.