Anti-MRSA agent discovery using Caenorhabditis elegans-based high-throughput screening
- 주제(키워드) antibiotic resistance , MRSA , Caenorhabditis elegans , high throughput screening , bacterial persisters , anti-infectives , host-pathogen interaction
- 주제(기타) Microbiology
- 설명문(일반) [Kim, Soo Min; Kim, Wooseong] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Seoul 03760, South Korea; [Escorbar, Iliana; Lee, Kiho; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios] Brown Univ, Rhode Isl Hosp, Div Infect Dis, Warren Alpert Med Sch, Providence, RI 02903 USA
- 등재 SCIE, SCOPUS, KCI등재
- 발행기관 MICROBIOLOGICAL SOCIETY KOREA
- 발행년도 2020
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000168945
- 본문언어 영어
- Published As https://dx.doi.org/10.1007/s12275-020-0163-8
- PubMed https://pubmed.ncbi.nlm.nih.gov/32462486
초록/요약
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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