Abstract
α-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 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 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 α-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.
Highlights
Staphylococcus aureus (S. aureus), one of the most common pathogens, is a critical cause of many local and systemic infections ranging from pneumonia, sepsis, and andocarditis, to osteomyelitis
The minimum inhibitory concentration (MIC) determination and growth curve assays were performed to determine the antibacterial activity of AE for S. aureus
The results of hemolysis assays showed that AE notably inhibited the hemolytic activity of the S. aureus supernatant in a dose-dependent manner when cocultured with bacteria
Summary
Staphylococcus aureus (S. aureus), one of the most common pathogens, is a critical cause of many local and systemic infections ranging from pneumonia, sepsis, and andocarditis, to osteomyelitis. Among these diseases, S. aureus pneumonia is one of the most serious ventilator-associated infections, with ∼10–25% mortality and, for some secondary infections, the rate can even reach 75% (Gillet et al, 2002; Del Giudice et al, 2011; Li et al, 2011; Chastre et al, 2014). Attenuation of S. aureus Pathogenicity by Aloe-emodin the multiresistance of MRSA has become more complicated, which typically results in a delay in clinical treatment (Mendes et al, 2013). Several studies have reported that targeting virulence factors typically results in weak pathogenicity of pathogens, suggesting that this may be a promising strategy in the treatment of S. aureus pneumonia (Qiu et al, 2012a,b; Wang et al, 2016)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
