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Aloe-emodin Attenuates Staphylococcus aureus Pathogenicity by Interfering With the Oligomerization of ?-Toxin.


ABSTRACT: ?-toxin, an essential virulence factor secreted by Staphylococcus aureus (S. aureus), is a critical exotoxin in multiple infections. In this study, we found that aloe-emodin (AE), a natural compound lacking anti-S. aureus activity, could inhibit the hemolytic activity of ?-toxin. Oligomerization assays, molecular dynamics simulations, and fluorescence-quenching analyses were used to determine the mechanism of this inhibition. The oligomerization of ?-toxin was restricted by the engagement of AE with K110, T112, and M113 of the toxin, which eventually resulted in inhibition of the hemolytic activity. Lactate dehydrogenase and live/dead assays demonstrated that AE decreased the injury of human lung epithelial cells (A549) and mouse lung macrophages (MH-S) mediated by S. aureus. Furthermore, treatment with AE showed robust protective effects in mice infected by S. aureus. These findings suggest that AE effectively inhibited the pore-forming activity of ?-toxin and showed a protective effect against S. aureus virulence in vitro and in vivo, which may provide a new strategy and new antibacterial agent for clinical treatment of S. aureus infections.

SUBMITTER: Jiang L 

PROVIDER: S-EPMC6530610 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Aloe-emodin Attenuates <i>Staphylococcus aureus</i> Pathogenicity by Interfering With the Oligomerization of α-Toxin.

Jiang Lanxiang L   Yi Tian T   Shen Ziying Z   Teng Zihao Z   Wang Jianfeng J  

Frontiers in cellular and infection microbiology 20190515


α-toxin, an essential virulence factor secreted by <i>Staphylococcus aureus</i> (<i>S. aureus</i>), is a critical exotoxin in multiple infections. In this study, we found that aloe-emodin (AE), a natural compound lacking anti-<i>S. aureus</i> activity, could inhibit the hemolytic activity of α-toxin. Oligomerization assays, molecular dynamics simulations, and fluorescence-quenching analyses were used to determine the mechanism of this inhibition. The oligomerization of α-toxin was restricted by  ...[more]

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