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Baicalin Weakens Staphylococcus aureus Pathogenicity by Targeting Sortase B.
- Source :
-
Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2018 Nov 30; Vol. 8, pp. 418. Date of Electronic Publication: 2018 Nov 30 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Staphylococcus aureus ( S. aureus ) is a human and other animal pathogen that contributes to the primary etiology of nosocomial pneumonia, a disease with high mortality rates and costs. Treatment of multidrug-resistant S. aureus infection is extremely challenging, and new therapeutic strategies beyond antibiotic treatment are needed. Anti-virulence agents that specifically target the molecular determinants of virulence may be a novel method for treating drug-resistant nosocomial infections. Sortase B (SrtB) is a crucial virulence factor in S. aureus and plays an important role during infection. In this study, we find that baicalin suppresses the activity of SrtB. Minimum inhibitory concentration and growth curve assays confirmed that baicalin has no anti- S. aureus properties. We performed live/dead, lactate dehydrogenase (LDH), adherence, and enzyme-linked immunosorbent assays to confirm that baicalin reduced human alveolar epithelial A549 cell injury caused by S. aureus , reduced the adherence of S. aureus to A549 cells, and significantly attenuated the inflammatory response of mouse macrophage J774 cells to S. aureus . Additionally, we were able to elucidate the binding mechanics and identify the interacting sites of baicalin and SrtB via a molecular dynamics simulation, site-directed mutagenesis, and fluorescence spectroscopy quenching. Finally, we confirmed that baicalin directly binds to the active center of SrtB, and the residues Asn <superscript>92</superscript> and Tyr <superscript>128</superscript> perform an important function in the interaction of SrtB and baicalin. Taken together, these data indicate that baicalin is a promising candidate to combat S. aureus infections.
- Subjects :
- A549 Cells drug effects
Adhesins, Bacterial drug effects
Aminoacyltransferases genetics
Aminoacyltransferases metabolism
Animals
Bacterial Proteins genetics
Bacterial Proteins metabolism
Binding Sites
Cysteine Endopeptidases genetics
Cysteine Endopeptidases metabolism
Humans
Inflammation
Macrophages drug effects
Methicillin-Resistant Staphylococcus aureus drug effects
Mice
Microbial Sensitivity Tests
Molecular Dynamics Simulation
Mutagenesis, Site-Directed
Protein Conformation drug effects
Staphylococcal Infections drug therapy
Staphylococcus aureus genetics
Virulence drug effects
Virulence Factors metabolism
Aminoacyltransferases antagonists & inhibitors
Anti-Bacterial Agents pharmacology
Bacterial Proteins antagonists & inhibitors
Enzyme Inhibitors pharmacology
Flavonoids pharmacology
Staphylococcus aureus drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2235-2988
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Frontiers in cellular and infection microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 30555803
- Full Text :
- https://doi.org/10.3389/fcimb.2018.00418