Rapid High-Throughput Assay Identified Gemcitabine and Derivatives As Potent Inhibitors Against Multidrug-Resistant Staphylococcus aureus
ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES(2022)
Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) are challenging pathogenic bacteria that can cause severe infection leading to high mortality rates. We found that both the oxacillin- and cefoxitin-resistant S. aureus strains isolated from clinic showed multidrug-resistant (MDR) characteristics. Through rapid high-throughput screen (HTS) of a compound library, gemcitabine and selen compounds were found to effectively inhibit S. aureus growth. For further improvement, we synthesized selen-containing gemcitabine that demonstrated relatively potent antimicrobial activity against several MDR MRSA in vitro. The HTS assay and gemcitabine selen derivative provided a useful tool to explore an effective molecular target to treat MDR MRSA.
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Key words
methicillin-resistant Staphylococcus aureus, multidrug resistance, gemcitabine, EZMTT-based HTS method, selen derivative
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