Subinhibitory concentrations of resveratrol reduce alpha-hemolysin production in Staphylococcus aureus isolates by downregulating saeRS

Abstract

Resveratrol is a natural phytoalexin. In recent studies, it has been shown to have beneficial effects on cardiovascular disease and cancer and has been deemed to have effective antiviral and immunomodulatory activities. Methicillin-resistant Staphylococcus aureus is a multidrug-resistant pathogen associated with skin and soft tissue infections. Alpha-hemolysin is known to play a key role in the symptoms caused by S. aureus, and the saeRS two-component system has been shown to be a major regulatory system of S. aureus virulence. The present study was designed to determine the effect of subinhibitory concentrations of resveratrol on the production of alpha-hemolysin in S. aureus. The effect of resveratrol on the transcription of S. aureus was studied by transcriptome sequencing. A total of 760 genes with >2-fold changes in expression were selected, including 479 upregulated genes and 281 downregulated genes. On the basis of transcriptome sequencing, the expression of alpha-hemolysin in the S. aureus strains of the resveratrol-treated group was downregulated. Our results showed that resveratrol weakly inhibited the growth of S. aureus strains, and subinhibitory concentration of resveratrol decreased the expression of hla and inhibited the regulation of saeRS. Hemolysis testing confirmed that resveratrol had an inhibitory effect on the hemolysis of rabbit erythrocytes infected with S. aureus strains in a dose-dependent manner. Resveratrol also decreased the hemolytic capacity by reducing the production of alpha-hemolysin. We found that resveratrol could decrease the expression of hla and reduce the secretion of alpha-hemolysin by downregulating saeRS. These findings have provided more evidence of the potential of resveratrol as a drug for resisting S. aureus infections.

Subinhibitory Concentrations of Fusidic Acid May Reduce the Virulence of S. aureus by Down-Regulating sarA and saeRS to Reduce Biofilm Formation and α-Toxin Expression

“…By RT-PCR, we found that the subinhibitory concentrations of fusidic acid down-regulated the expression of saeRS at the mRNA level. This is consistent with previous research in our laboratory (Duan et al, 2018;Jin et al, 2018) in that saeRS can downregulate the production of α-toxin. For the part of the biofilm, it was found by the crystal violet staining method that the S. aureus biofilm with fusidic acid was down-regulated, which is consistent with the previous study (Siala et al, 2018).…”

“…In recent years, it has been reported in the literature that fusidic acid has an inhibitory effect on the biofilm formation of S. aureus (Siala et al, 2018), but the mechanism is not clear. Inspired by the subinhibitory concentrations of mupirocin and resveratrol, which can downregulate the virulence of S. aureus in our previous study (Duan et al, 2018;Jin et al, 2018), we attempted to study the effect of subinhibitory concentrations of fusidic acid on the virulence of S. aureus.…”

“…However, whether the use of subinhibitory antibiotics can effectively reduce the resistance rate of S. aureus is still controversial (Bhattacharya et al, 2017), and further research is needed. S. aureus produces a variety of toxins (Duan et al, 2018), wherein α-toxin acts as an indispensable part of the pathogenicity of S. aureus leading to tissue damage. The α-toxin is 33.2 kDa of exocrine protein encoded by hla gene, which is also a poreforming toxin that causes cell damage and death (Bhakdi and Tranum-Jensen, 1991).…”

Steroid Derivatives as Potential Antimicrobial Agents against Staphylococcus aureus Planktonic Cells

“…These results are in accord with literature data. Duan et al [34] showed subinhibitory concentration of resveratrol decreased the expression of hla and inhibited the regulation of saeRS. Subinhibitory concentrations of thymol significantly inhibited the transcription of hla, sea, and seb in S. aureus and acted partly through the agr locus [35].…”

Antimicrobial and Antivirulence Action of Eugenia brejoensis Essential Oil in vitro and in vivo Invertebrate Models

“…In this sense, bacteria are frequently exposed to Sub-MIC of the antimicrobial agent and these conditions could result in mutagenesis and release of microbial virulence factors (Andersson and Hughes, 2014;Jo and Ahn, 2016;Larsen et al, 2016;Huijbers et al, 2019). Thus, it is important to evaluate the effects of the antimicrobial agents in pathways related to mutagenesis and virulence (Hobdey et al, 2017;Duan et al, 2018). We first showed that EbEO did not induce the expression of recA which is the first gene in the SOS response.…”