Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation

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.

Raf-Kinase Inhibitor Gw5074 Shows Antibacterial Activity Against Methicillin-Resistant Staphylococcus Aureus and Potentiates the Activity of Gentamicin

“…Therefore, C. elegans is useful as an alternative host to study innate immunity and to screen for pathogenic factors [36]. Our lab, in collaboration with others, successfully used this nematode in the C. elegans infection model to screen and identify new antimicrobial agents and compounds that affect pathogen virulence or modulate the innate immune response of nematodes during pathogen infection [17,[37][38][39][40].…”

Beyond Traditional Antimicrobials: A Caenorhabditis elegans Model for Discovery of Novel Anti-infectives

“…qRT-PCR analysis of the host PMK-1 and DAF-16-regulated antimicrobial genes confirmed a significant positive modulation of these genes in S. aureus -infected worms exposed to O. stamineus extract. Further studies also revealed eupatorin as the major bioactive ingredient that contributed to the immunomodulation effect of O. stamineus (Kong et al, 2014a). In a separate study, O. stamineus extract also modulated the cellular immune response in vitro (Alshawsh et al, 2012).…”

Caenorhabditis elegans in high-throughput screens for anti-infective compounds

“…The authors showed that the protection provided by colistin is dependent on the p38 MAP kinase innate immune pathway, as well as the stress-response mediators, DAF-16/FOXO and SKN-1/Nrf [36]. Another study found that a natural product extract has immunostimulatory activity in C. elegans and protects nematodes from S. aureus infection [37]. …”