Abstract
Staphylococcus aureus (S. aureus), a Gram-positive bacteria, is an incurable cause of hospital and community-acquired infections. Inhibition bacterial virulence is a viable strategy against S. aureus infections based on the multiple virulence factors secreted by S. aureus. Alpha-hemolysin (Hla) plays a crucial role in bacteria virulence without affecting bacterial viability. Here, we identified that 7,8-Dihydroxyflavone (7,8-DHF), a natural compound, was able to decrease the expression of and did not affect the in vitro growth of S. aureus USA300 at a concentration of 32 μg/mL. It was verified by western blot and RT-qPCR that the natural compound could inhibit the transcription and translation of Hla. Further mechanism studies revealed that 7,8-DHF has a negative effect on transcriptional regulator agrA and RNAIII, preventing the upregulation of virulence gene. Cytotoxicity assays showed that 7,8-DHF did not produce significant cytotoxicity to A549 cells. Animal experiments showed that the combination of 7,8-DHF and vancomycin had a more significant therapeutic effect on S. aureus infection, reflecting the synergistic effect of 7,8-DHF with antibiotics. In conclusion, 7,8-DHF was able to target Hla to protect host cells from hemolysis while limiting the development of bacterial resistance.
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The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was partly supported by a grant from the Science and Technology Development Plan Project (2019) of Jilin Province Science and Technology Department (20190103080JH), “Xinglin Scholar Project” of Changchun University of Chinese Medicine (2019) and “Thirteenth Five-Year Plan” of Science and Technology Project of Education Department of Jilin Province (No. JJKH20200906KJ).
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NB, XC, XR, ZY, MJ, XC, CL, YL, LW, TJ: material preparation, data collection and analysis; LW and YC: drafting of the manuscript; CZ, BW and XS: revision of the manuscript; YZ, WS, ZS conception and desigining of the experiments. All authors read and approved the final manuscript.
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Bian, N., Chen, X., Ren, X. et al. 7,8-Dihydroxyflavone attenuates the virulence of Staphylococcus aureus by inhibiting alpha-hemolysin. World J Microbiol Biotechnol 38, 200 (2022). https://doi.org/10.1007/s11274-022-03378-2
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DOI: https://doi.org/10.1007/s11274-022-03378-2