The protection effect of rhodionin against methicillin-resistant Staphylococcus aureus-induced pneumonia through sortase A inhibition

被引:15
作者
Wang, Xingye [1 ,2 ]
Luan, Yanhe [3 ]
Hou, Juan [1 ]
Jiang, Tao [1 ]
Zhao, Yicheng [1 ]
Song, Wu [1 ]
Wang, Li [1 ]
Kong, Xiangri [1 ,3 ]
Guan, Jiyu [4 ]
Song, Danning [1 ]
Wang, Bingmei [1 ]
Li, Mingquan [1 ,2 ,3 ]
机构
[1] Changchun Univ Chinese Med, Changchun, Peoples R China
[2] Changchun Univ Chinese Med, Affiliated Hosp 3, Changchun, Peoples R China
[3] Changchun Univ Chinese Med, Affiliated Hosp, Changchun, Peoples R China
[4] Jilin Univ, Coll Vet Med, Key Lab Zoonosis, Minist Educ, Changchun, Peoples R China
关键词
Anti-virulence; MRSA; Rhodionin; Sortase A; SURFACE-PROTEINS; CELL-WALL; PHENOLIC-COMPOUNDS; BACTERIAL; FLAVONOIDS; EMERGENCE; SUBSTRATE; UPDATE; ROOT;
D O I
10.1007/s11274-022-03457-4
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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 mu g/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 K-A value of 6.22 x10(5) 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. [GRAPHICS] .
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页数:14
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