AUTHOR=Jiang Lanxiang , Yi Tian , Shen Ziying , Teng Zihao , Wang Jianfeng 

TITLE=Aloe-emodin Attenuates Staphylococcus aureus Pathogenicity by Interfering With the Oligomerization of α-Toxin

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2019.00157

DOI=10.3389/fcimb.2019.00157

ISSN=2235-2988

ABSTRACT=<p>α-toxin, an essential virulence factor secreted by <italic>Staphylococcus aureus</italic> (<italic>S. aureus</italic>), is a critical exotoxin in multiple infections. In this study, we found that aloe-emodin (AE), a natural compound lacking anti-<italic>S. aureus</italic> 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 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 <italic>S. aureus</italic>. Furthermore, treatment with AE showed robust protective effects in mice infected by <italic>S. aureus</italic>. These findings suggest that AE effectively inhibited the pore-forming activity of α-toxin and showed a protective effect against <italic>S. aureus</italic> virulence <italic>in vitro</italic> and <italic>in vivo</italic>, which may provide a new strategy and new antibacterial agent for clinical treatment of <italic>S. aureus</italic> infections.</p>