Inhibition of alpha-hemolysin expression by resveratrol attenuates Staphylococcus aureus virulence

Microb Pathog. 2019 Feb:127:85-90. doi: 10.1016/j.micpath.2018.11.027. Epub 2018 Nov 20.

Abstract

Staphylococcus aureus is an important zoonotic pathogen that causes a variety of life-threatening diseases. The increasing emergence of drug resistance further complicates the treatment of S. aureus infections. The critical role of alpha-hemolysin (Hla) in virulence renders this toxin an ideal target for the development of anti-infective agents for S. aureus. Here, We found that resveratrol, a natural compound widely found in fruits without antibacterial activity, could effectively inhibit Hla expression via down-regulating the transcription of hla, the gene that encodes Hla, and RNAIII, the effector molecule of the agr system. The addition of resveratrol to a co-culture system of S. aureus and A549 cells significantly alleviated bacteria-mediated cellular injury. Furthermore, treatment with resveratrol effectively protected mice from S. aureus pneumonia. Our results established resveratrol as an effective Hla inhibitor that reduces Hla expression without antimicrobial activity and can be further developed into novel therapeutics against S. aureus infections.

Keywords: Alpha-hemolysin; Anti-infective agent; Resveratrol; Staphylococcus aureus.

MeSH terms

  • A549 Cells
  • Animals
  • Bacterial Toxins / antagonists & inhibitors*
  • Coculture Techniques
  • Disease Models, Animal
  • Enzyme Inhibitors / metabolism*
  • Hemolysin Proteins / antagonists & inhibitors*
  • Humans
  • Mice
  • Pneumonia, Staphylococcal / drug therapy
  • Pneumonia, Staphylococcal / prevention & control*
  • Resveratrol / metabolism*
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / pathogenicity*
  • Treatment Outcome
  • Virulence / drug effects

Substances

  • Bacterial Toxins
  • Enzyme Inhibitors
  • Hemolysin Proteins
  • staphylococcal alpha-toxin
  • Resveratrol