Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

BMC Complementary and Alternative Medicine

Sheila Nathan⁴  Man-Wah Tan²  Noorsaadah Abd Rahman³  Wageeh A Yehye¹  Cin Kong⁴ 

[1] Nanotechnology & Catalysis Research Centre (NANOCAT), Block 3A, Institute of Postgraduate Studies Building, University of Malaya, Kuala Lumpur, Malaysia;Current Affiliation: Department of Infectious Diseases Genentech, 1 DNA Way, 11-316 Mail Stop 33, South San Francisco, USA;Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia;School of Biosciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor, Malaysia

关键词: Anti-infectives;    C. elegans;    S. aureus;   

Others  :  1220395
DOI  :  10.1186/1472-6882-14-4

 received in 2013-08-15, accepted in 2014-01-03,  发布年份 2014

【 摘 要 】

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, Orthosiphonstamineus 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.

【 授权许可】

   
2014 Kong et al.; licensee BioMed Central Ltd.

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