Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific RNA interference (RNAi) revealed that HPX-2 functionally localizes to the hypodermis of the worm. In congruence with this observation, hpx-2 mutant animals possessed a slightly weaker cuticle structure, indicated by higher permeability to a DNA dye, but exhibited no obvious morphological defects. In addition, fluorescent labeling of HPX-2 revealed its expression in the pharynx, an organ in which BLI-3 also resides. Interestingly, loss of HPX-2 increased intestinal colonization of E. faecalis, suggesting its role in the pharynx may limit intestinal colonization. Moreover, disruption of a catalytic residue in the peroxidase domain of HPX-2 resulted in decreased survival on E. faecalis, indicating its peroxidase activity is required for pathogen resistance. Finally, RNA-seq analysis of an hpx-2 mutant revealed changes in genes encoding for cuticle structural components under the non-pathogenic conditions. Under pathogenic conditions, genes involved in infection response were differentially regulated to a greater degree, likely due to the increased microbial burden. In conclusion, the characterization of the heme-peroxidase, HPX-2, revealed that it contributes to C. elegans pathogen resistance through a role in generating cuticle material in the hypodermis and pharynx.
","abstract_html":"<p>Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In <em>Caenorhabditis elegans,</em> a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen<em> Enterococcus faecalis,</em> likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (<strong>H</strong>eme-<strong>P</strong>ero<strong>X</strong>idase 2), is required for resistance against some, but not all pathogens. Tissue specific RNA interference (RNAi) revealed that HPX-2 functionally localizes to the hypodermis of the worm. In congruence with this observation, <em>hpx-2 </em>mutant animals possessed a slightly weaker cuticle structure, indicated by higher permeability to a DNA dye, but exhibited no obvious morphological defects. In addition, fluorescent labeling of HPX-2 revealed its expression in the pharynx, an organ in which BLI-3 also resides. Interestingly, loss of HPX-2 increased intestinal colonization of <em>E. faecalis, </em>suggesting its role in the pharynx may limit intestinal colonization. Moreover, disruption of a catalytic residue in the peroxidase domain of HPX-2 resulted in decreased survival on <em>E. faecalis</em>, indicating its peroxidase activity is required for pathogen resistance. Finally, RNA-seq analysis of an <em>hpx-2</em> mutant revealed changes in genes encoding for cuticle structural components under the non-pathogenic conditions. Under pathogenic conditions, genes involved in infection response were differentially regulated to a greater degree, likely due to the increased microbial burden. In conclusion, the characterization of the heme-peroxidase, HPX-2, revealed that it contributes to <em>C. elegans</em> pathogen resistance through a role in generating cuticle material in the hypodermis and pharynx.</p>","abstract_has_math":false,"creators":["Liu, Yi",""],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Danielle Garsin","Ambro van Hoof","Swathi Arur"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-12-01T08:00:00Z","date_published":"2018-12-01T08:00:00Z","updated_at":"2026-07-24T05:48:59Z","subjects":["C. elegans","heme peroxidase","immunity","pathogen","Medicine and Health Sciences"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/918","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Danielle Garsin","Ambro van Hoof","Swathi Arur"]},{"key":"dc:creator","label":"Author","values":["Liu, Yi",""]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-06-14T07:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["C. elegans","heme peroxidase","immunity","pathogen","Medicine and Health Sciences"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/918"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific RNA interference (RNAi) revealed that HPX-2 functionally localizes to the hypodermis of the worm. In congruence with this observation, hpx-2 mutant animals possessed a slightly weaker cuticle structure, indicated by higher permeability to a DNA dye, but exhibited no obvious morphological defects. In addition, fluorescent labeling of HPX-2 revealed its expression in the pharynx, an organ in which BLI-3 also resides. Interestingly, loss of HPX-2 increased intestinal colonization of E. faecalis, suggesting its role in the pharynx may limit intestinal colonization. Moreover, disruption of a catalytic residue in the peroxidase domain of HPX-2 resulted in decreased survival on E. faecalis, indicating its peroxidase activity is required for pathogen resistance. Finally, RNA-seq analysis of an hpx-2 mutant revealed changes in genes encoding for cuticle structural components under the non-pathogenic conditions. Under pathogenic conditions, genes involved in infection response were differentially regulated to a greater degree, likely due to the increased microbial burden. In conclusion, the characterization of the heme-peroxidase, HPX-2, revealed that it contributes to C. elegans pathogen resistance through a role in generating cuticle material in the hypodermis and pharynx.
"]},{"key":"dc:title","label":"Title","values":["Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens"]}]}],"canonical_facts":{"dc:contributor":["Danielle Garsin","Ambro van Hoof","Swathi Arur"],"dc:creator":["Liu, Yi",""],"dc:date.available":["2019-06-14T07:00:00Z"],"dc:description.abstract":["Heme-containing peroxidases are important components of innate immunity. Many of them functionally associate with NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes by using the hydrogen peroxide they generate in downstream reactions. In Caenorhabditis elegans, a ShkT-containing peroxidase, SKPO-1, and the dual oxidase, BLI-3, contribute to resistance against the human pathogen Enterococcus faecalis, likely functioning in conjunction with each other. However, the exact mechanism(s) by which peroxidases and NOX/DUOXs contribute to pathogen resistance remain unclear. Here, we demonstrated that another peroxidase, HPX-2 (Heme-PeroXidase 2), is required for resistance against some, but not all pathogens. Tissue specific RNA interference (RNAi) revealed that HPX-2 functionally localizes to the hypodermis of the worm. In congruence with this observation, hpx-2 mutant animals possessed a slightly weaker cuticle structure, indicated by higher permeability to a DNA dye, but exhibited no obvious morphological defects. In addition, fluorescent labeling of HPX-2 revealed its expression in the pharynx, an organ in which BLI-3 also resides. Interestingly, loss of HPX-2 increased intestinal colonization of E. faecalis, suggesting its role in the pharynx may limit intestinal colonization. Moreover, disruption of a catalytic residue in the peroxidase domain of HPX-2 resulted in decreased survival on E. faecalis, indicating its peroxidase activity is required for pathogen resistance. Finally, RNA-seq analysis of an hpx-2 mutant revealed changes in genes encoding for cuticle structural components under the non-pathogenic conditions. Under pathogenic conditions, genes involved in infection response were differentially regulated to a greater degree, likely due to the increased microbial burden. In conclusion, the characterization of the heme-peroxidase, HPX-2, revealed that it contributes to C. elegans pathogen resistance through a role in generating cuticle material in the hypodermis and pharynx.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/918"],"dc:subject":["C. elegans","heme peroxidase","immunity","pathogen","Medicine and Health Sciences"],"dc:title":["Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:48:59Z"}