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Article Publish Status: FREE
Abstract Title:

Taxifolin, an Inhibitor of Sortase A, Interferes With the Adhesion of Methicillin-Resistant.

Abstract Source:

Front Microbiol. 2021 ;12:686864. Epub 2021 Jul 6. PMID: 34295320

Abstract Author(s):

Li Wang, Guangming Wang, Han Qu, Kai Wang, Shisong Jing, Shuhan Guan, Liyan Su, Qianxue Li, Dacheng Wang

Article Affiliation:

Li Wang

Abstract:

The evolution and spread of methicillin-resistant(MRSA) poses a significant hidden risk to human public health. The majority of antibiotics used clinically have become mostly ineffective, and so the development of novel anti-infection strategies is urgently required. Since() cysteine transpeptidase sortase A (SrtA) mediates the surface-anchoring of proteins to its surface, compounds that inhibit SrtA are considered potential antivirulence treatments. Herein, we report on the efficacy of the potent SrtA inhibitor taxifolin (Tax), a flavonoid compound isolated from Chinese herbs. It was able to reversibly block the activity of SrtA with an ICof 24.53± 0.42 μM. Tax did not display toxicity toward mammalian cells orat a concentration of 200μM. In addition, Tax attenuated the virulence-related phenotype of SrtAby decreasing the adherence of, reducing the formation of a biofilm, and anchoring ofprotein A on its cell wall. The mechanism of the SrtA-Tax interaction was determined using a localized surface plasmon resonance assay. Subsequent mechanistic studies confirmed that Asp-170 and Gln-172 were the principal sites on SrtA with which it binds to Tax. Importantly,experiments demonstrated that Tax protects mice against pneumonia induced by lethal doses of MRSA, significantly improving their survival rate and reducing the number of viablein the lung tissue. The present study indicates that Tax is a useful pioneer compound for the development of novel agents againstinfections.

Study Type : In Vitro Study

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