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Updated: May 4, 2026
A High-throughput, High-content, Liquid-based C. elegans Pathosystem
Published on: July 1, 2018
Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model
Cin Kong, Wageeh A Yehye, Noorsaadah Abd Rahman
1School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia. sheila@ukm.my.
Background:
The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.
Methods:
We established a C. elegans - S. aureus liquid-based assay to screen for potential anti-infectives against S. aureus. The assay was utilized to screen 37 natural extracts and 29 synthetic compounds for the ability to extend the lifespan of infected nematodes. Disc diffusion and MIC microdilution tests were used to evaluate the anti-microbial properties of these natural extracts and synthetic compounds whilst in vivo bacterial CFU within the C. elegans gut were also enumerated.
Results:
We screened a total of 37 natural extracts and 29 synthetic compounds for anti-infective properties. The screen successfully revealed 14 natural extracts from six plants (Nypa fruticans, Swietenia macrophylla, Curcuma longa, Eurycoma longifolia, Orthosiphon stamineus and Silybum eburneum) and one marine sample (Faunus ater) that improved the survival of S. aureus-infected worms by at least 2.8-fold as well as 14 synthetic compounds that prolonged the survival of S. aureus-infected nematodes by 4-fold or greater. An anti-microbial screen of all positive hits demonstrated that 8/28 hits had no effect on S. aureus growth. Of these 8 candidates, 5 of them also protected the worms from MRSA infection. We also noted that worms exposed to N. fruticans root and O. stamineus leaf extracts showed reduced intestinal colonization by live S. aureus. This suggests that these extracts could possibly activate host immunity to eliminate the bacteria or interfere with factor/s that prevents pathogen accumulation.
Conclusion:
We have successfully demonstrated the utility of this liquid-based screen to identify anti-infective substances that prolong S. aureus-infected host survival without affecting bacterial cell viability.
Insights
New anti-infectives were identified to combat methicillin-resistant Staphylococcus aureus (MRSA) by extending host survival without killing bacteria. This research offers novel strategies against persistent MRSA infections.
Area of Science:
- Microbiology and Infectious Diseases
- Drug Discovery and Development
- Host-Pathogen Interactions
Background:
- Limited antibiotic options necessitate novel therapeutic strategies against methicillin-resistant Staphylococcus aureus (MRSA).
- Alternative approaches include targeting virulence pathways or modulating host immunity to combat MRSA infections.
Purpose of the Study:
- To establish and utilize a C. elegans-based liquid assay for screening anti-infective compounds against S. aureus.
- To identify natural extracts and synthetic compounds that enhance host survival during S. aureus infection.
Main Methods:
- A C. elegans-S. aureus liquid-based assay screened 37 natural extracts and 29 synthetic compounds.
- Disc diffusion, MIC microdilution, and in vivo bacterial CFU enumeration assessed antimicrobial properties and efficacy.
- Host survival in infected nematodes was the primary screening endpoint.
Main Results:
- 14 natural extracts and 14 synthetic compounds significantly prolonged the survival of S. aureus-infected nematodes.
- Eight compounds showed no direct antimicrobial effect on S. aureus growth, with five of these protecting nematodes.
- Specific extracts (N. fruticans, O. stamineus) reduced intestinal bacterial colonization, suggesting immune modulation or anti-adherence mechanisms.
Conclusions:
- The C. elegans liquid-based screen effectively identifies anti-infective substances that enhance host survival without direct antimicrobial action.
- This approach provides a valuable tool for discovering novel anti-virulence or host-modulating agents against S. aureus.
