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

Research output: Contribution to journalReview articlepeer-review

9 Scopus citations

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. elegans-based screening strategy as a paradigm shift screening platform.

Original languageEnglish
Pages (from-to)431-444
Number of pages14
JournalJournal of Microbiology
Volume58
Issue number6
DOIs
StatePublished - 1 Jun 2020

Bibliographical note

Publisher Copyright:
© 2020, The Microbiological Society of Korea.

Keywords

  • Caenorhabditis elegans
  • MRSA
  • anti-infectives
  • antibiotic resistance
  • bacterial persisters
  • high throughput screening
  • host-pathogen interaction

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