Biology subjects

Espejo, L. S.

Publications and source records attributed to Espejo, L. S..

3 recordsLinked to original sources

bioRxiv2024

The Emerging Role of 3-Hydroxyanthranilic Acid on C. elegans Aging Immune Function

3-hydroxyanthranilic acid (3HAA) is considered to be a fleeting metabolic intermediate along tryptophan catabolism through the kynurenine pathway. 3HAA and the rest of the kynurenine pathway have been linked to immune response in mammals yet whether it is detrimental or advantageous is a point of contention. Recently we have shown that accumulation of this metabolite, either through supplementation or prevention of its degradation, extends healthy lifespan in C. elegans and mice, while the mechanism remained unknown. Utilizing C. elegans as a model we investigate how 3HAA and haao-1 inhibition impact the host and the potential pathogens. What we find is that 3HAA improves host immune function with aging and serves as an antimicrobial against gram-negative bacteria. Regulation of 3HAAs antimicrobial activity is accomplished via tissue separation. 3HAA is synthesized in the C. elegans hypodermal tissue, localized to the site of pathogen interaction within the gut granules, and degraded in the neuronal cells. This tissue separation creates a new possible function for 3HAA that may give insight to a larger evolutionarily conserved function within the immune response. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/574394v2_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@3d74d1org.highwire.dtl.DTLVardef@c079c7org.highwire.dtl.DTLVardef@7b1f2eorg.highwire.dtl.DTLVardef@13c3eb3_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

SICKO: Systematic Imaging of Caenorhabtidis Killing Organisms

Caenorhabditis elegans are an important model system for research on host-microbe interaction. Their rapid life cycle, short lifespan, and transparent body structure allow simple quantification of microbial load and the influence of microbial exposure on host survival. C. elegans host-microbe interaction studies typically examine group survival and infection severity at fixed timepoints. Here we present an imaging pipeline, Systematic Imaging of Caenorhabditis Killing Organisms (SICKO), that allows longitudinal characterization of microbes colonizing isolated C. elegans, enabling dynamic tracking of tissue colonization and host survival in the same animals. Using SICKO, we show that Escherichia coli or Pseudomonas aeruginosa gut colonization dramatically shortens C. elegans lifespan and that immunodeficient animals lacking pmk-1 are more susceptible to colonization but display similar colony growth relative to wild type. SICKO opens new avenues for detailed research into bacterial pathogenesis, the benefits of probiotics, and the role of the microbiome in host health.

immunology↗

bioRxiv2023

Inhibition of haao-1 enhances oxidative stress response by activating hormetic redox signaling in C. elegans.

3-hydroxyanthranilate 3,4-dioxygenase (HAAO) is an intermediate enzyme in the conversion from tryptophan (TRP) to nicotinamide adenine dinucleotide (NAD+) via the kynurenine pathway. The kynurenine pathway is the sole de novo NAD+ biosynthetic pathway from ingested tryptophan. Inhibition of several enzymatic steps in the kynurenine pathway increases lifespan in Drosophila melanogaster, Saccharomyces cerevisiae, and Caenorhabditis elegans. Knockout or knockdown of haao-1, the C. elegans gene encoding HAAO, or supplementation of its substrate metabolite 3-hydroxyanthranilic acid (3HAA), has been shown to promote healthy lifespan extension; however, the underlying mechanism remains unknown. In the present study, we report that haao-1 knockdown induces oxidative stress resistance against several reactive oxygen species (ROS) inducing agents by activating the Nrf2/SKN-1 oxidative stress response pathway. An examination of the redox state of animals with reduced haao-1 suggests that activation of the Nrf2/SKN-1 pathway is mediated by shifting the balance toward generation of ROS, generating a hormetic effect. Our results identify a novel mechanism for an endogenous metabolite (3HAA) that activates the oxidative stress response. These results provide a conceptual basis by which modulation of the kynurenine pathway can promote healthy aging and enhanced stress resistance. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/528568v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@1563682org.highwire.dtl.DTLVardef@114917dorg.highwire.dtl.DTLVardef@15bc7f2org.highwire.dtl.DTLVardef@a42023_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIKnockdown of haao-1 promotes oxidative stress resistance. C_LIO_LIKnockdown of haao-1 activates the Nrf2/SKN-1 oxidative stress response. C_LIO_LIThe shift in redox balance in haao-1 knockout animals suggests a hormetic mechanism for oxidative stress resistance. C_LI

molecular biology↗