Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is a zoonotic antibiotic-resistant pathogen that negatively impacts society from medical, veterinary, and societal standpoints. The search for alternative therapeutic strategies and innovative anti-infective agents is urgently needed. Among the pathogenic mechanisms of Staphylococcus aureus (S. aureus), sortase A is a virulence factor of great concern because it is highly linked with the ability of MRSA to invade the host. In this study, we identified that rhodionin, a natural compound of flavonoid glucosides, effectively inhibited the activity of SrtA without affecting the survival and growth of bacteria, and its half maximal inhibitory concentration (IC50) value was 22.85 μg/mL. In vitro, rhodionin prominently attenuated the virulence-related phenotype of SrtA by reducing the adhesion of S. aureus to fibrinogen, reducing the capacity of protein A (SpA) on the bacterial surface and biofilm formation. Subsequently, fluorescence quenching and molecular docking were performed to verify that rhodionin directly bonded to SrtA molecule with KA value of 6.22 × 105 L/mol. More importantly, rhodionin showed a significant protective effect on mice pneumonia model and improved the survival rate of mice. According to the above findings, rhodionin achieved efficacy in the treatment of MRSA-induced infections, which holds promising potential to be developed into a candidate used for MRSA-related infections.
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The datasets generated during and/or analysed 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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ML, BW and DS designed the study. XW and XK participated in the expression and purification of the SrtA protein. YL and JH participated in the SrtA inhibitor screening and SrtA-related assay. TJ and XK participated in the WB and fluorescence quenching assay. JG and XK participated in the animal experiment and molecular docking. LW and YZ conducted the analysis. WS and XW drafted the manuscript. All authors read and approved the final manuscript.
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The animal work in this report was approved by the Experimental Animal Ethics Committee of Changchun University of Chinese Medicine, and it complied with the regulations on the use of experimental animals.
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Wang, X., Luan, Y., Hou, J. et al. The protection effect of rhodionin against methicillin-resistant Staphylococcus aureus-induced pneumonia through sortase A inhibition. World J Microbiol Biotechnol 39, 18 (2023). https://doi.org/10.1007/s11274-022-03457-4
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DOI: https://doi.org/10.1007/s11274-022-03457-4