P. aeruginosa liquid-based pathogenesis triggers HLH-30-dependent metabolic rewiring in C. elegans
- 1Rice University
Abstract
Innate immunity is the first line of defense against invading pathogens and is essential for maintaining host survival. While the majority of innate immunity studies have focused on pathogen recognition and antimicrobial responses, increasing evidence suggests that lipid metabolism plays a fundamental role in shaping immune function. Understanding how these metabolic pathways contribute to immunity is crucial in the context of bacterial infections caused by opportunistic pathogens such as Pseudomonas aeruginosa. Host defense against P. aeruginosa requires the coordination of innate immune and metabolic responses; however, the mechanisms linking lipid metabolism to pathogen resistance remain poorly understood. Research into the relationship between lipid homeostasis and innate immunity may reveal factors governing host-pathogen interactions and identify novel strategies to enhance resistance to infection. Here, we demonstrate that P. aeruginosa liquid-based pathogenesis (LK-Pa) triggers a shift in host metabolism which differs from the one observed in response to agar-based pathogenesis. Our bioinformatic analyses revealed a highly similar metabolic profile (enrichment of lipid metabolism) in worms exposed to LK-Pa or the iron chelator phenanthroline, suggesting a shared host response to iron deprivation. We further characterized the host genetic factors driving this metabolic shift and established their importance for host defense against LK-Pa as well as liquid-based pathogenesis by Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Notably, our results indicate that LK-Pa triggers host lipid droplet depletion, an upstream component that leads to increased {beta}-oxidation. Finally, we demonstrate that LK-Pa triggers repression of MXL-3 which results in HLH-30-dependent metabolic rewiring.
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BibTeX
@misc{armendariz2026aeruginosa,
title = {{P. aeruginosa liquid-based pathogenesis triggers HLH-30-dependent metabolic rewiring in C. elegans}},
author = {L. Armendariz and E. Tjahjono and Y. Acevedo and F. Vaca and J. Lowder and A. Singh and N. Singh and A. V. Revtovich and A. High and E. Park and N. V. Kirienko},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749215},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749215v1},
note = {CC BY-ND},
}
RIS
TY - UNPB
TI - P. aeruginosa liquid-based pathogenesis triggers HLH-30-dependent metabolic rewiring in C. elegans
AU - L. Armendariz
AU - E. Tjahjono
AU - Y. Acevedo
AU - F. Vaca
AU - J. Lowder
AU - A. Singh
AU - N. Singh
AU - A. V. Revtovich
AU - A. High
AU - E. Park
AU - N. V. Kirienko
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749215
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749215v1
AB - Innate immunity is the first line of defense against invading pathogens and is essential for maintaining host survival. While the majority of innate immunity studies have focused on pathogen recognition and antimicrobial responses, increasing evidence suggests that lipid metabolism plays a fundamental role in shaping immune function. Understanding how these metabolic pathways contribute to immunity is crucial in the context of bacterial infections caused by opportunistic pathogens such as Pseudomonas aeruginosa. Host defense against P. aeruginosa requires the coordination of innate immune and metabolic responses; however, the mechanisms linking lipid metabolism to pathogen resistance remain poorly understood. Research into the relationship between lipid homeostasis and innate immunity may reveal factors governing host-pathogen interactions and identify novel strategies to enhance resistance to infection. Here, we demonstrate that P. aeruginosa liquid-based pathogenesis (LK-Pa) triggers a shift in host metabolism which differs from the one observed in response to agar-based pathogenesis. Our bioinformatic analyses revealed a highly similar metabolic profile (enrichment of lipid metabolism) in worms exposed to LK-Pa or the iron chelator phenanthroline, suggesting a shared host response to iron deprivation. We further characterized the host genetic factors driving this metabolic shift and established their importance for host defense against LK-Pa as well as liquid-based pathogenesis by Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Notably, our results indicate that LK-Pa triggers host lipid droplet depletion, an upstream component that leads to increased {beta}-oxidation. Finally, we demonstrate that LK-Pa triggers repression of MXL-3 which results in HLH-30-dependent metabolic rewiring.
ER -