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Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting α-toxin expression

Abstract

α-Toxin, one of the best known pore-forming proteins produced by Staphylococcus aureus (S. aureus), is a critical virulence factor in multiple infections. The necessity of α-toxin for S. aureus pathogenicity suggests that this toxin is an important target for the development of a potential treatment strategy. In this study, we showed that lysionotin, a natural compound, can inhibit the hemolytic activity of culture supernatants by S. aureus by reducing α-toxin expression. Using real-time PCR analysis, we showed that transcription of hla (the gene encoding α-toxin) and agr (the locus regulating hla) was significantly inhibited by lysionotin. Lactate dehydrogenase and live/dead assays indicated that lysionotin effectively protected human alveolar epithelial cells against S. aureus, and in vivo studies also demonstrated that lysionotin can protect mice from pneumonia caused by S. aureus. These findings suggest that lysionotin is an efficient inhibitor of α-toxin expression and shows significant protection against S. aureus in vitro and in vivo. This study supports a potential strategy for the treatment of S. aureus infection by inhibiting the expression of virulence factors and indicates that lysionotin may be a potential treatment for S. aureus pneumonia.

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Acknowledgments

This study was funded by the National Basic Research Program of China (No. 2013CB127205) and the National Natural Science Foundation of China (grant 31602109).

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Correspondence to Xuming Deng or Jianfeng Wang.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Teng, Z., Shi, D., Liu, H. et al. Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting α-toxin expression. Appl Microbiol Biotechnol 101, 6697–6703 (2017). https://doi.org/10.1007/s00253-017-8417-z

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Keywords

  • Staphylococcus aureus
  • Lysionotin
  • α-Toxin
  • Pneumonia