Baicalin Weakens Staphylococcus aureus Pathogenicity by Targeting Sortase B.

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 Asn92 and Tyr128 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.

• Authors: Guizhen Wang, Yawen Gao, Hongsu Wang, Xiaodi Niu, Jianfeng Wang
• Journal: Frontiers in cellular and infection microbiology (Front Cell Infect Microbiol) Vol. 8 Pg. 418 ( 2018) ISSN: 2235-2988 [Electronic] Switzerland
• PMID: 30555803 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adhesins, Bacterial
• Anti-Bacterial Agents
• Bacterial Proteins
• Enzyme Inhibitors
• Flavonoids
• Virulence Factors
• sortase B
• baicalin
• Aminoacyltransferases
• Cysteine Endopeptidases

Topics

• A549 Cells (drug effects)
• Adhesins, Bacterial (drug effects)
• Aminoacyltransferases (antagonists & inhibitors, genetics, metabolism)
• Animals
• Anti-Bacterial Agents (pharmacology)
• Bacterial Proteins (antagonists & inhibitors, genetics, metabolism)
• Binding Sites
• Cysteine Endopeptidases (genetics, metabolism)
• Enzyme Inhibitors (pharmacology)
• Flavonoids (pharmacology)
• 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 (drug effects, genetics)
• Virulence (drug effects)
• Virulence Factors (metabolism)