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Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
Published on: January 3, 2020
Dracorhodin Perochlorate attenuates Staphylococcus aureus USA300 virulence by decreasing α-toxin expression
Yumin Liu1,2, Dongxue Shi3, Yan Guo3
1College of Animal Science and Technology, Jilin Agricultural University, Changchun, 130118, China.
Abstract:
α-Toxin, a pore-forming toxin secreted by most Staphylococcus aureus, plays critical role in the pathogenesis associated with various infectious diseases. The USA300 which is a major international epidemic methicilin-resisrant S. aureus has spread rapidly to multiple countries and become an emerging public health concern. In this study, the in vitro efficacy of Dracorhodin Perochlorate (DP) against USA300 virulence was evaluated. Using susceptibility testing, immunoblots, rabbit blood haemolytic assay and real-time RT-PCR, we observed that the α-toxin production was decreased when USA300 was co-cultured with different sub-inhibitory concentration of DP. Further, the protective effect of DP against USA300-mediated injury of human alveolar epithelial cells (A549) and MH-S cells was evaluated by cytotoxicity assays, and the result revealed that DP, at final concentration of 16 µg/ml, is a potent antagonist for USA300-mediated cell damage. Importantly, those beneficial effects might partially correlate with hla and RNAIII suppression by DP, leading to the inhibition of α-toxin production in culture supernatant. Overall, these results suggest that DP could attenuate the virulence of USA300 by decreasing α-toxin production without inhibiting bacterial growth, and this compound may represent an ideal candidate for the development of anti-virulence agent combating S. aureus infection.
Insights
Dracorhodin Perochlorate (DP) reduces α-toxin production in Staphylococcus aureus USA300, a major public health concern. This compound protects against bacterial-induced cell damage without affecting bacterial growth, offering a potential anti-virulence strategy.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Staphylococcus aureus, particularly the USA300 strain, is a significant cause of infectious diseases globally.
- α-Toxin is a key virulence factor produced by S. aureus, contributing to disease pathogenesis.
- Developing anti-virulence strategies that target toxin production is crucial for combating antibiotic-resistant infections.
Purpose of the Study:
- To evaluate the in vitro efficacy of Dracorhodin Perochlorate (DP) against the virulence of Staphylococcus aureus USA300.
- To determine if DP can inhibit α-toxin production and protect host cells from S. aureus-mediated damage.
- To explore the potential of DP as an anti-virulence agent against S. aureus infections.
Main Methods:
- Susceptibility testing, immunoblots, and rabbit blood haemolytic assays were used to assess α-toxin production.
- Real-time RT-PCR was employed to analyze the expression of virulence genes (hla and RNAIII).
- Cytotoxicity assays were performed on human alveolar epithelial cells (A549) and MH-S cells to evaluate DP's protective effects.
Main Results:
- DP significantly decreased α-toxin production in USA300 at sub-inhibitory concentrations.
- DP demonstrated a protective effect against USA300-mediated cell damage in A549 and MH-S cells at 16 µg/ml.
- The beneficial effects of DP were associated with the suppression of hla and RNAIII, leading to reduced α-toxin release.
Conclusions:
- Dracorhodin Perochlorate (DP) attenuates the virulence of Staphylococcus aureus USA300 by inhibiting α-toxin production.
- DP acts as a potent antagonist against USA300-mediated cell damage without affecting bacterial growth.
- DP shows promise as a novel anti-virulence agent for combating S. aureus infections.

