Ampelopsin attenuates Staphylococcus aureus Alpha-Toxin-Induced Lung Injury

• Published in: Microbial pathogenesis 2023-10, Vol.183, p.106316-106316, Article 106316
• Main Authors: Wang, Yi, Tang, Mulan, Deng, Haojian, Hong, Zhengshan, Liang, Zhi, Huang, Yumei, Zeng, Chunhui, Yang, Ke
• Format: Article
• Language: English
• Subjects: Acute lung injury; Alpha-toxin; Ampelopsin; Mortality rate; Staphylococcus aureus
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2023.106316

Staphylococcus aureus is a prevalent cause of lung infections in hospitals and communities, and can cause a wide spectrum of human infections. Due to the bottleneck caused by antibiotic resistance and substantial increases in morbidity and mortality, targeting the virulence factors released by S. aureus as an alternative prevention and treatment method has become a promising approach. Ampelopsin, a component of vine tea, has promising potential for treating S. aureus-induced acute lung injury. In this study, the effects of ampelopsin were investigated on a mouse model of acute lung injury established using S. aureus 8325–4 and the α-hemolysin (hla) silent strain DU1090. The hla silent strain did not cause mortality in mice, whereas lethal and sublethal concentrations of S. aureus 8325–4 caused high mortality. Notably, ampelopsin treatment protected against mortality stemming from S. aureus infection. Ampelopsin yielded enhancements in lung barrier function, decreased total protein leakage in the alveolar lavage fluid, and modulated inflammatory signaling pathway-related proteins, thereby reducing the release of pro-inflammatory factors and improving respiratory dysfunction. Moreover, ampelopsin prevented the upregulation of ADAM10 activity, leading to E-cadherin mucin cleavage. In conclusion, our findings establish the key role of alpha -toxin in infectious lung injury in S. aureus and provide support for ampelopsin as an effective therapeutic approach to improve lung injury. [Display omitted] •Alpha-Toxin secreted by S. aureus facilitates bacterial colonization of the lungs for infection.•Alpha-Toxin secreted by S. aureus was able to activate the metalloproteinase ADAM10 and cleave E-cadherin.•Compared with the alpha-toxin silent strain DU1090, S. aureus 8325-4 secreting alpha-toxin was able to cause massive leakage of proteins in alveolar lavage fluid.•Ampelopsin has been shown to attenuate infectious lung injury through a combination of anti-inflammatory, antimicrobial, and alpha-toxin inhibition effects.