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KMID : 0880220200580060431
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Journal of Microbiology
2020 Volume.58 No. 6 p.431 ~ p.444
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Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening
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Kim Soo-Min
Escorbar Iliana
Lee Ki-Ho
Fuchs Beth Burgwyn
Mylonakis Eleftherios
Kim Woo-Seong
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Abstract
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Staphylococcus aureus is a leading cause of hospital- and community-acquired infections. Despite current advances in antimicrobial chemotherapy, the infections caused by S. aureus remain challenging due to their ability to readily develop resistance. Indeed, antibiotic resistance, exemplified by methicillin-resistant S. aureus (MRSA) is a top threat to global health security. Furthermore, the current rate of antibiotic discovery is much slower than the rate of antibiotic-resistance development. It seems evident that the conventional in vitro bacterial growth-based screening strategies can no longer effectively supply new antibiotics at the rate needed to combat bacterial antibiotic-resistance. To overcome this antibiotic resistance crisis, screening assays based on host?pathogen interactions have been developed. In particular, the free-living nematode Caenorhabditis elegans has been used for drug screening against MRSA. In this review, we will discuss the general principles of the C. elegans-based screening platform and will highlight its unique strengths by comparing it with conventional antibiotic screening platforms. We will outline major hits from high-throughput screens of more than 100,000 small molecules using the C. elegans?MRSA infection assay and will review the mode-of-action of the identified hit compounds. Lastly, we will discuss the potential of a C. elegans-based screening strategy as a paradigm shift screening platform.
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KEYWORD
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antibiotic resistance, MRSA, Caenorhabditis elegans, high throughput screening, bacterial persisters, anti-infectives, host-pathogen interaction
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