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.
Bibliographical noteFunding Information:
This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT) (No. 2020R1C1C1008842, 2018R1A5A2025286 and 2017M3A9E4077234) and the Ewha Womans University Research Grant of 2019 to W.K. and National Institutes of Health Grant P01AI083214 to E.M.
© 2020, The Microbiological Society of Korea.
- Caenorhabditis elegans
- antibiotic resistance
- bacterial persisters
- high throughput screening
- host-pathogen interaction