Attenuating Staphylococcus aureus Virulence by Targeting Flotillin Protein Scaffold Activity
Autor: | Charlotte Wermser, Daniel Lopez, Stephanie T. Stengel, Lara Kricks, Gudrun Koch, Ana Yepes, Ivan C. Acosta |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Scaffold protein Staphylococcus aureus RNase P Phosphorylcholine 030106 microbiology Clinical Biochemistry Virulence Biology medicine.disease_cause Biochemistry Small Molecule Libraries 03 medical and health sciences Mice Membrane Microdomains Bacterial Proteins Drug Resistance Multiple Bacterial Two-Hybrid System Techniques Drug Discovery Endoribonucleases medicine Animals Molecular Biology Pharmacology Mice Inbred BALB C RNA Ribosomal 5S Membrane Proteins Staphylococcal Infections Cell biology Survival Rate Disease Models Animal RNA Bacterial Membrane protein Transfer RNA Molecular Medicine Female Degradosome Protein Multimerization Function (biology) |
Zdroj: | Cell chemical biology. 24(7) |
ISSN: | 2451-9448 |
Popis: | Summary Scaffold proteins are ubiquitous chaperones that bind proteins and facilitate physical interaction of multi-enzyme complexes. Here we used a biochemical approach to dissect the scaffold activity of the flotillin-homolog protein FloA of the multi-drug-resistant human pathogen Staphylococcus aureus . We show that FloA promotes oligomerization of membrane protein complexes, such as the membrane-associated RNase Rny, which forms part of the RNA-degradation machinery called the degradosome. Cells lacking FloA had reduced Rny function and a consequent increase in the targeted sRNA transcripts that negatively regulate S. aureus toxin expression. Small molecules that altered FloA oligomerization also reduced Rny function and decreased the virulence potential of S. aureus in vitro, as well as in vivo, using invertebrate and murine infection models. Our results suggest that flotillin assists in the assembly of protein complexes involved in S. aureus virulence, and could thus be an attractive target for the development of new antimicrobial therapies. |
Databáze: | OpenAIRE |
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