Abstract
Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host.
Original language | English |
---|---|
Pages (from-to) | 644-655 |
Number of pages | 12 |
Journal | Biology Open |
Volume | 3 |
Issue number | 7 |
DOIs | |
Publication status | Published - 15 Jul 2014 |
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Keywords
- Anti-infective
- C. elegans
- Immunomodulation
- O. stamineus
- S. aureus
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)
Cite this
Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation. / Kong, Cin; Tan, Man Wah; Nathan, Sheila.
In: Biology Open, Vol. 3, No. 7, 15.07.2014, p. 644-655.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation
AU - Kong, Cin
AU - Tan, Man Wah
AU - Nathan, Sheila
PY - 2014/7/15
Y1 - 2014/7/15
N2 - Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host.
AB - Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host.
KW - Anti-infective
KW - C. elegans
KW - Immunomodulation
KW - O. stamineus
KW - S. aureus
UR - http://www.scopus.com/inward/record.url?scp=84978481320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84978481320&partnerID=8YFLogxK
U2 - 10.1242/bio.20148334
DO - 10.1242/bio.20148334
M3 - Article
AN - SCOPUS:84978481320
VL - 3
SP - 644
EP - 655
JO - Biology Open
JF - Biology Open
SN - 2046-6390
IS - 7
ER -