Biochanin A as an α-hemolysin inhibitor for combating methicillin-resistant Staphylococcus aureus infection

World J Microbiol Biotechnol. 2021 Nov 27;38(1):6. doi: 10.1007/s11274-021-03182-4.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. In S. aureus, α-hemolysin is an important virulence factor as it contributes to the capacity of the bacteria to infect the host. Here, we showed that biochanin A (bioA), an isoflavone present in red clover, cabbage and alfalfa, effectively inhibited hemolytic activity at a dose as low as 32 μg/mL. Further, western blot and RT-qPCR data showed that bioA reduced the production and expression of MRSA hemolysin in a dose-dependent manner. In addition, when different concentrations of bioA were added to a coculture system of A549 cells and S. aureus, it could significantly decrease cell injury. Importantly, the in vivo study showed that bioA could protect mice from pneumonia caused by a lethal dose of MRSA, as evidenced by improving their survival and reducing the number of bacterial colonies in lung tissues, the secretion of hemolysin into alveolar lavage fluid and the degree of pulmonary edema. In conclusion, biochanin A protected the host from MRSA infection by inhibiting the expression of the hemolysin of MRSA, which may provide experimental evidence for its development to a potential anti-MRSA drug.

Keywords: Antivirulence; Biochanin A; Methicillin-resistant Staphylococcus aureus; α-Hemolysin.

MeSH terms

  • A549 Cells
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Bacterial / drug effects
  • Genistein / administration & dosage*
  • Genistein / pharmacology
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism*
  • Hemolysis / drug effects
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Mice
  • Pneumonia / drug therapy*
  • Pneumonia / microbiology
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Hemolysin Proteins
  • Genistein
  • biochanin A