[MINIREIVEW] Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening

Soo Min Kim; Iliana Escorbar; Kiho Lee; Beth Burgwyn Fuchs; Eleftherios Mylonakis; Wooseong Kim

doi:10.1007/s12275-020-0163-8

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[MINIREIVEW] Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening: Soo Min Kim ¹, Iliana Escorbar ², Kiho Lee ², Beth Burgwyn Fuchs ², Eleftherios Mylonakis ², Wooseong Kim ¹; Journal of Microbiology 2020;58(6):431-444.
DOI: https://doi.org/10.1007/s12275-020-0163-8
Published online: May 27, 2020

¹College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea, ²Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, 02903, USA¹College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea, ²Division of Infectious Diseases, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, Rhode Island, 02903, USA

Corresponding author: Wooseong Kim , Tel: +82-2-3277-3372,

Received: 30 March 2020 • Revised: 4 May 2020 • Accepted: 6 May 2020

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Abstract

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. elegansbased screening strategy as a paradigm shift screening platform.

Keywords: anti microbial resistance (AMR);boronic acids;diazabicyclooctanes (DBO);serine-β-lactamase, metallo-β-lactamases (MBL);β-lactamase inhibitors

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[MINIREIVEW] Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening

J. Microbiol. 2020;58(6):431-444. Published online May 27, 2020

DOI: https://doi.org/10.1007/s12275-020-0163-8

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