| Title | [MINIREIVEW] Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening |
|---|---|
| Author | Soo Min Kim1, Iliana Escorbar2, Kiho Lee2, Beth Burgwyn Fuchs2, Eleftherios Mylonakis2, and Wooseong Kim1* |
| Address | 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, USA |
| Bibliography | Journal of Microbiology, 58(6),431–444, 2020, |
| DOI | 10.1007/s12275-020-0163-8 |
| Key Words | antibiotic resistance, MRSA, Caenorhabditis elegans, high throughput screening, bacterial persisters, antiinfectives, host-pathogen interaction |
| 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. |