The Regulatory Small RNA MarS Supports Virulence of Streptococcus pyogenes

Small regulatory RNAs (sRNAs) play a role in the control of bacterial virulence gene expression. In this study, we investigated an sRNA that was identified in Streptococcus pyogenes (group A Streptococcus , GAS) but is conserved throughout various streptococci. In a deletion strain, expression of mg...

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Published in:	Scientific reports Vol. 7; no. 1; pp. 12241 - 15
Main Authors:	Pappesch, Roberto, Warnke, Philipp, Mikkat, Stefan, Normann, Jana, Wisniewska-Kucper, Aleksandra, Huschka, Franziska, Wittmann, Maja, Khani, Afsaneh, Schwengers, Oliver, Oehmcke-Hecht, Sonja, Hain, Torsten, Kreikemeyer, Bernd, Patenge, Nadja
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 25-09-2017 Nature Publishing Group
Subjects:	38 38/70 38/77 5' Untranslated Regions 631/326/41/2531 631/337/384/521 64 64/60 82 82/58 Animal Structures - microbiology Animal Structures - pathology Animals Bacterial Load Bacterial Proteins - biosynthesis Bacterial Proteins - genetics Cells, Cultured Deletion mutant Disease Models, Animal Electrophoretic Mobility Shift Assay Gene Deletion Gene expression Gene Expression Profiling Gene Expression Regulation, Bacterial Humanities and Social Sciences Humans Keratinocytes Kidneys Liver Macrophages - immunology Macrophages - microbiology Mice, Inbred BALB C multidisciplinary Nucleic Acid Hybridization Oxidative stress Phagocytosis Proteome - analysis Proteomes Ribonucleic acid RNA RNA, Small Untranslated - genetics RNA, Small Untranslated - metabolism Science Science (multidisciplinary) Spleen Streptococcal Infections - microbiology Streptococcal Infections - pathology Streptococcus infections Streptococcus pyogenes Streptococcus pyogenes - genetics Streptococcus pyogenes - pathogenicity Transcription Virulence factors Virulence Factors - biosynthesis
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Summary:	Small regulatory RNAs (sRNAs) play a role in the control of bacterial virulence gene expression. In this study, we investigated an sRNA that was identified in Streptococcus pyogenes (group A Streptococcus , GAS) but is conserved throughout various streptococci. In a deletion strain, expression of mga , the gene encoding the multiple virulence gene regulator, was reduced. Accordingly, transcript and proteome analyses revealed decreased expression of several Mga-activated genes. Therefore, and because the sRNA was shown to interact with the 5′ UTR of the mga transcript in a gel-shift assay, we designated it MarS for m ga - a ctivating r egulatory s RNA. Down-regulation of important virulence factors, including the antiphagocytic M-protein, led to increased susceptibility of the deletion strain to phagocytosis and reduced adherence to human keratinocytes. In a mouse infection model, the marS deletion mutant showed reduced dissemination to the liver, kidney, and spleen. Additionally, deletion of marS led to increased tolerance towards oxidative stress. Our in vitro and in vivo results indicate a modulating effect of MarS on virulence gene expression and on the pathogenic potential of GAS.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2045-2322 2045-2322
DOI:	10.1038/s41598-017-12507-z