دورية أكاديمية
أعرض في EDS

The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in Staphylococcus aureus.

التفاصيل البيبلوغرافية
العنوان: The Small RNA Teg41 Regulates Expression of the Alpha Phenol-Soluble Modulins and Is Required for Virulence in Staphylococcus aureus.
المؤلفون: Zapf RL; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Wiemels RE; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Keogh RA; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Holzschu DL; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Howell KM; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Trzeciak E; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Caillet AR; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., King KA; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Selhorst SA; Department of Biological Sciences, Ohio University, Athens, Ohio, USA., Naldrett MJ; Proteomics and Metabolomics Facility, Center for Biotechnology, University of Nebraska Lincoln, Lincoln, Nebraska, USA., Bose JL; Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, Kansas, USA., Carroll RK; Department of Biological Sciences, Ohio University, Athens, Ohio, USA carrolr3@ohio.edu.
المصدر: MBio [mBio] 2019 Feb 05; Vol. 10 (1). Date of Electronic Publication: 2019 Feb 05.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, D.C. : American Society for Microbiology
مواضيع طبية MeSH: Gene Expression Regulation, Bacterial*, Bacterial Toxins/*biosynthesis , RNA, Bacterial/*metabolism , RNA, Small Untranslated/*metabolism , Staphylococcus aureus/*genetics , Staphylococcus aureus/*growth & development , Virulence Factors/*biosynthesis, Abscess/microbiology ; Abscess/pathology ; Animals ; Disease Models, Animal ; Genetic Complementation Test ; Hemolysis ; Humans ; Mice ; Sequence Deletion ; Staphylococcal Infections/microbiology ; Staphylococcal Infections/pathology ; Virulence
مستخلص: Small RNAs (sRNAs) remain an understudied class of regulatory molecules in bacteria in general and in Gram-positive bacteria in particular. In the major human pathogen Staphylococcus aureus , hundreds of sRNAs have been identified; however, only a few have been characterized in detail. In this study, we investigate the role of the sRNA Teg41 in S. aureus virulence. We demonstrate that Teg41, an sRNA divergently transcribed from the locus that encodes the cytolytic alpha phenol-soluble modulin (αPSM) peptides, plays a critical role in αPSM production. Overproduction of Teg41 leads to an increase in αPSM levels and a corresponding increase in hemolytic activity from S. aureus cells and cell-free culture supernatants. To identify regions of Teg41 important for its function, we performed an in silico RNA-RNA interaction analysis which predicted an interaction between the 3' end of Teg41 and the αPSM transcript. Deleting a 24-nucleotide region from the S. aureus genome, corresponding to the 3' end of Teg41, led to a 10-fold reduction in αPSM-dependent hemolytic activity and attenuation of virulence in a murine abscess model of infection. Restoration of hemolytic activity in the Teg41Δ3' strain was possible by expressing full-length Teg41 in trans Restoration of hemolytic activity was also possible by expressing the 3' end of Teg41, suggesting that this region of Teg41 is necessary and sufficient for αPSM-dependent hemolysis. Our results show that Teg41 is positively influencing αPSM production, demonstrating for the first time regulation of the αPSM peptides by an sRNA in S. aureus IMPORTANCE The alpha phenol-soluble modulins (αPSMs) are among the most potent toxins produced by Staphylococcus aureus Their biological role during infection has been studied in detail; however, the way they are produced by the bacterial cell is not well understood. In this work, we identify a small RNA molecule called Teg41 that plays an important role in αPSM production by S. aureus Teg41 positively influences αPSM production. The importance of Teg41 is highlighted by the fact that a strain containing a deletion in the 3' end of Teg41 produces significantly less αPSMs and is attenuated for virulence in a mouse abscess model of infection. As the search for new therapeutic strategies to combat S. aureus infection proceeds, Teg41 may represent a novel target.
(Copyright © 2019 Zapf et al.)
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معلومات مُعتمدة: R01 AI121073 United States AI NIAID NIH HHS; R21 AI128376 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: PSM; Staphylococcus aureus; Teg41; phenol-soluble modulin; regulatory RNA; sRNA
المشرفين على المادة: 0 (Bacterial Toxins)
0 (RNA, Bacterial)
0 (RNA, Small Untranslated)
0 (Virulence Factors)
0 (staphylococcal delta toxin)
تواريخ الأحداث: Date Created: 20190207 Date Completed: 20190405 Latest Revision: 20200225
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6428751
DOI: 10.1128/mBio.02484-18
PMID: 30723124
قاعدة البيانات: MEDLINE
الوصف
تدمد:2150-7511
DOI:10.1128/mBio.02484-18