Heme Peroxidase Hpx-2 Protects Caenorhabditis Elegans From Pathogens

<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>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation (PhD)

Year dc:date.available

2018

Authors dc:creator

• Liu, Yi
• <p><a href="https://urldefense.proofpoint.com/v2/url?u=https-3A__orcid.org_0000-2D0001-2D5758-2D9619&d=DwMCAA&c=6vgNTiRn9_pqCD9hKx9JgXN1VapJQ8JVoF8oWH1AgfQ&r=KUQ-wwC5yCtlQtHKFpOi1xFE3AkmyO5Anx1QI4pqWVU&m=vWtvKzvpTDToqv7H4BvDvkXHoKJ5YMIb5VVriL61t7A&s=w_xNM7LRE0gi8NKBpydTv0noUxBKwBBOqlQeUGGzHzw&e=" target="_blank">0000-0001-5758-9619</a></p>

Contributors dc:contributor

• Danielle Garsin
• Ambro van Hoof
• Swathi Arur

• C. elegans
• heme peroxidase
• immunity
• pathogen
• Medicine and Health Sciences

Repository record dc:identifier

https://digitalcommons.library.tmc.edu/utgsbs_dissertations/918

OAI identifier oai:identifier

oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-1966