Distinct members of the C. elegans CeMbio reference microbiota exert cryptic virulence and infection protection [preprint]
Student AuthorsXavier Gonzalez
Academic ProgramImmunology and Microbiology
UMass Chan AffiliationsMicrobiology and Physiological Systems
Morningside Graduate School of Biomedical Sciences
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AbstractMicrobiotas are complex microbial communities that colonize specific niches in the host and provide essential organismal functions that are important in health and disease. A key aspect is the ability of each distinct community member to promote or impair host health, alone or in the context of the community, in hosts with varied levels of immune competence. Understanding such interactions is limited by the complexity and experimental accessibility of current systems and models. Recently, a reference twelve-member microbiota for the model organism C. elegans, known as CeMbio, was defined to aid the dissection of conserved host-microbiota interactions. Understanding the physiological impact of the CeMbio bacteria on C. elegans is in its infancy. Here, we show the differential ability of each CeMbio bacterial species to activate innate immunity through the conserved PMK-1/p38 MAPK, ACh/WNT, and HLH-30/TFEB pathways. Using immunodeficient animals, we uncovered several examples of bacterial 'cryptic' virulence, or virulence that was masked by the host defense response. The ability to activate the PMK-1/p38 pathway did not correlate with bacterial virulence in wild type or immunodeficient animals. In contrast, ten out of twelve species activated HLH-30/TFEB, and most showed virulence towards hlh-30-deficient animals. In addition, we identified Pseudomonas lurida as a pathogen in wild type animals, and Acinetobacter guillouiae as avirulent despite activating all three pathways. Moreover, short pre-exposure to A. guillouiae promoted host survival of infection with P. lurida, which was dependent on PMK-1/p38 MAPK and HLH-30/TFEB. These results suggest that the microbiota of C. elegans is rife with "opportunistic" pathogens, and that HLH-30/TFEB is a fundamental and key host protective factor. Furthermore, they support the idea that bacteria like A. guillouiae evolved the ability to induce host innate immunity to improve host fitness when confronted with pathogens, providing new insights into how colonization order impacts host health.
SourceGonzalez X, Irazoqui JE. Distinct members of the C. elegans CeMbio reference microbiota exert cryptic virulence and infection protection. bioRxiv [Preprint]. 2023 Nov 5:2023.11.02.565327. doi: 10.1101/2023.11.02.565327. PMID: 37961109; PMCID: PMC10635080.
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/52799
NotesThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
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Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 International