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Article Publish Status: FREE
Abstract Title:

Curcumin protects mice from Staphylococcus aureus pneumonia by interfering with the self-assembly process ofα-hemolysin.

Abstract Source:

Sci Rep. 2016 ;6:28254. Epub 2016 Jun 27. PMID: 27345357

Abstract Author(s):

Jianfeng Wang, Xuan Zhou, Wenhua Li, Xuming Deng, Yanhong Deng, Xiaodi Niu

Article Affiliation:

Jianfeng Wang

Abstract:

α-hemolysin (Hla) is a self-assembling extracellular protein secreted as a soluble monomer by most Staphylococcus aureus strains and is an essential virulence factor for the pathogenesis of various S. aureus infections. Here, we show that curcumin (CUR), a natural compound with weak anti-S. aureusactivity, can inhibit the hemolysis induced by Hla. Molecular dynamics simulations, free energy calculations, and mutagenesis assays were further employed for the Hla-CUR complex to determine the mechanism of such inhibition. The analysis of this combined approach indicated that the direct binding CUR to Hla blocks the conformational transition of Hla from the monomer to the oligomer, leading to an inhibition of Hla hemolytic activity. We also found that the addition of CUR significantly attenuated Hla-mediated injury of human alveolar cell (A549) co-cultured with S. aureus. The in vivo data further demonstrated that treatment with CUR protects mice from pneumonia caused by S. aureus, including methicillin-resistant strains (MRSA). These findings suggest that CUR inhibits the pore-forming activity of Hla through a novel mechanism, which would pave the way for the development of new and more effective antibacterial agents to combat S. aureus pneumonia.

Study Type : Animal Study

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Sayer Ji
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