Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting α-toxin expression

Teng, Zihao; Shi, Dan; Liu, Huanyu; Shen, Ziying; Zha, Yonghong; Li, Wenhua; Deng, Xuming

doi:10.1007/s00253-017-8417-z

Cited by 30 publications

(18 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Natural herbs are increasingly being shown to have antitoxic activity. For example, Lysionotin targeted inhibition of α-toxin expression to decrease the pathogenicity of S. aureus (Teng et al, 2017) and Chalcone reduced the virulence of S. aureus by targeting sortase A and α-toxin (Zhang et al, 2017). These reports were consistent with our finding that PRAE-a have significant antihemolytic activity against S. aureus α-toxin (Figure 2).…”

Section: Discussionsupporting

confidence: 89%

Paeoniflorin Derivative in Paeoniae Radix Aqueous Extract Suppresses Alpha-Toxin of Staphylococcus aureus

Liu

Zhang

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

The emergence and dissemination of bacterial infections is paralyzing our public health systems worldwide. Worse still, there are no effective antibiotics against bacterial toxins, which facilitate the infection. Natural herbs that target bacterial toxins may be a better choice for therapy of infectious diseases. However, most natural drugs present unknown compositions and unclear mechanisms. Here we demonstrated that the Chinese herb Paeoniae Radix aqueous extract (PRAE) could suppress alpha-toxin (α-toxin) of Staphylococcus aureus. We observed that the paeoniflorin derivative (PRAE-a) derivative in PRAE significantly abolished the hemolytic activity of S. aureus α-toxin. The analyses of high-performance liquid chromatography (HPLC), mass spectrometer (MS), Fourier transform infrared spectrometer (FTIR), and nuclear magnetic resonance (NMR) showed that PRAE-a was a glycoside compound with a paeoniflorin nucleus. We further found that PRAE-a disrupted the pore-forming ability of α-toxin by prevention of the dimer to heptamer. Therefore, PRAE-a proved to be an effective therapy for S. aureus lung infections in mice by inhibiting α-toxin. Collectively, these results highlighted that PRAE-a can be used as an antibacterial agent to attenuate S. aureus virulence by targeting α-toxin.

show abstract

Section: Discussionsupporting

confidence: 89%

Paeoniflorin Derivative in Paeoniae Radix Aqueous Extract Suppresses Alpha-Toxin of Staphylococcus aureus

Liu

Zhang

et al. 2021

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…α-Toxin activity determination was used to determine the inhibitory effect of fusidic acid on the release of α-toxin. The experimental method is based on the previous literature and has been slightly modified (Teng et al, 2017). S. aureus strains were cultured at 37 • C in TSB containing different concentrations of fusidic acid and no fusidic acid.…”

Section: α-Toxin Activity Determinationmentioning

confidence: 99%

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

Liu

Shen

et al. 2020

Front. Microbiol.

View full text Add to dashboard Cite

Staphylococcus aureus is an important pathogen in hospital and community infections. Fusidic acid is particularly effective in treating skin and wound infections caused by staphylococci. The purpose of our study was to clarify the effect of fusidic acid on the biofilm formation and α-toxin expression of S. aureus at subinhibitory concentrations [1/64, 1/32, and 1/16 × minimum inhibitory concentration (MIC)]. A total of 504 genes greater than a twofold or less than twofold change in expression of S. aureus effected by subinhibitory concentrations of fusidic acid were found, including 232 up-regulated genes and 272 down-regulated genes, which were determined by transcriptome sequencing. Our results showed subinhibitory concentrations of fusidic acid significantly inhibited the expression of hla, spa, icaA, and cidA at the mRNA level in clinical S. aureus strains tested. And subinhibitory concentrations of fusidic acid can significantly reduce the hemolysis activity and α-toxin production of S. aureus. In addition, the subinhibitory concentrations of fusidic acid significantly inhibited biofilm formation, autolysis, cell aggregation, and polysaccharide intercellular adhesin (PIA) production of S. aureus. Moreover, fusidic acid effectively reduces the damage of mouse skin lesion area. Furthermore, fusidic acid reduced the expression of the two-component regulatory system saeRS and staphylococcal accessory gene regulator (sarA). In conclusion, our results suggested that the 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, which will provide a theoretical basis for the clinical treatment of S. aureus infection. This is the first report that fusidic acid has an inhibitory effect on the virulence of S. aureus, and this broadens the clinical application of fusidic acid.

show abstract

“…Coumarin derivatives have displayed activity against S. aureus and Bacillus anthracis DNA helicases [7]. Further reports have described the efficacy of intraperitoneal injections of a synthetic dicoumarin derivative in septicemic mice [8] and hypodermic injections of lysionotin in mouse pneumonia model [9], confirming the potential use of natural products as leads for new drugs.…”

Section: Introductionmentioning

confidence: 99%

Prenylated flavonoid-enriched fraction from Maclura tinctoria shows biological activity against Staphylococcus aureus and protects Galleria mellonella larvae from bacterial infection

Almeida

Rodrigues

Paulino

et al. 2019

BMC Complement Altern Med

View full text Add to dashboard Cite

Background The Atlantic Forest biome extends along the entire Brazilian coast and is home to approximately 20,000 plant species, many of which are endemic; it is considered one of the hotspot regions of the planet. Several of these species are sources of natural products with biological activities that are still unknown. In this study, we evaluated the antimicrobial activity of 90 extracts derived from native Atlantic Forest tree species against Staphylococcus aureus , an important human and veterinary pathogen. Methods Extracts from native Atlantic Forest tree species were evaluated for their antimicrobial activity against S. aureus by in vitro standard methods. Phytochemical fractionation of the extract from Maclura tinctoria was performed by liquid-liquid partitioning. LC-DAD-ESI-MS was used for identification of constituents in the most active fraction. Damage of cells and alterations in the permeability of cell membrane were determined by atomic force microscopy (AFM) and crystal violet uptake assay, respectively. In vivo antimicrobial activity was evaluated using Galleria mellonella larvae infected with S. aureus with survival data collected using the Kaplan-Meier method. Results Among the organic or aqueous extracts tested here, 26 showed biological activity. Eight species showed relevant results, with a minimum inhibitory concentration (MIC) below 1 mg/mL. Antibacterial activity was registered for three species for the first time. An organic extract from Maclura tinctoria leaves showed the lowest MIC (0.08 mg/mL). Fractionation of this extract by liquid-liquid partitioning led to obtaining fraction 11FO d with a MIC of 0.04 mg/mL. This fraction showed strong activity against veterinary S. aureus isolates and contributed to the increased survival of Galleria mellonella larvae infected with S. aureus ATCC 29213. The bacterial surface was not altered by the presence of 11FO d, and no cell membrane damage was detected. The LC-DAD-ESI/MS analyses identified prenylated flavonoids as the major constituents responsible for the antibacterial activity of this active extract. Conclusion A fraction enriched in prenylated isoflavones and flavanones from M. tinctoria showed in vitro and in vivo efficacy as antistaphylococcal agents. These findings justify the need for further research to elucidate the mechanisms of action of these compounds.

show abstract

Lysionotin attenuates Staphylococcus aureus pathogenicity by inhibiting α-toxin expression

Cited by 30 publications

References 22 publications

Paeoniflorin Derivative in Paeoniae Radix Aqueous Extract Suppresses Alpha-Toxin of Staphylococcus aureus

Paeoniflorin Derivative in Paeoniae Radix Aqueous Extract Suppresses Alpha-Toxin of Staphylococcus aureus

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

Prenylated flavonoid-enriched fraction from Maclura tinctoria shows biological activity against Staphylococcus aureus and protects Galleria mellonella larvae from bacterial infection

Contact Info

Product

Resources

About