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.
Citations
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