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

Cin Kong, Wageeh A. Yehye, Noorsaadah Abd Rahman, Man Wah Tan, Sheila Nathan

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number4
JournalBMC Complementary and Alternative Medicine
Volume14
DOIs
Publication statusPublished - 6 Jan 2014

Fingerprint

Caenorhabditis elegans
Staphylococcus aureus
Orthosiphon
Methicillin-Resistant Staphylococcus aureus
Infection
Microbial Viability
Eurycoma
Cell Survival
Meliaceae
Curcuma
Survival
Plant Extracts
Anti-Infective Agents
Virulence
Immunity
Anti-Bacterial Agents
Bacteria
Growth

Keywords

  • Anti-infectives
  • C. elegans
  • S. aureus

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model. / Kong, Cin; Yehye, Wageeh A.; Abd Rahman, Noorsaadah; Tan, Man Wah; Nathan, Sheila.

In: BMC Complementary and Alternative Medicine, Vol. 14, 4, 06.01.2014.

Research output: Contribution to journalArticle

@article{955a5ac48c49469e89e41efe6333dfe5,
title = "Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model",
abstract = "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.",
keywords = "Anti-infectives, C. elegans, S. aureus",
author = "Cin Kong and Yehye, {Wageeh A.} and {Abd Rahman}, Noorsaadah and Tan, {Man Wah} and Sheila Nathan",
year = "2014",
month = "1",
day = "6",
doi = "10.1186/1472-6882-14-4",
language = "English",
volume = "14",
journal = "BMC Complementary and Alternative Medicine",
issn = "1472-6882",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

AU - Kong, Cin

AU - Yehye, Wageeh A.

AU - Abd Rahman, Noorsaadah

AU - Tan, Man Wah

AU - Nathan, Sheila

PY - 2014/1/6

Y1 - 2014/1/6

N2 - 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.

AB - 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.

KW - Anti-infectives

KW - C. elegans

KW - S. aureus

UR - http://www.scopus.com/inward/record.url?scp=84891550643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891550643&partnerID=8YFLogxK

U2 - 10.1186/1472-6882-14-4

DO - 10.1186/1472-6882-14-4

M3 - Article

VL - 14

JO - BMC Complementary and Alternative Medicine

JF - BMC Complementary and Alternative Medicine

SN - 1472-6882

M1 - 4

ER -