{"id":{"repo_id":"uthsc","oai_identifier":"oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2563"},"canonical_url":"https://search.dev.ndltd.org/etd/uthsc/oai:digitalcommons.library.tmc.edu:utgsbs_dissertations-2563","repository":{"repo_id":"uthsc","name":"University of Texas Health Science Center at Houston","base_url":"https://digitalcommons.library.tmc.edu/do/oai/"},"display":{"title":"A tractable nematode model for the emerging fungal pathogen, Candida auris","abstract":"<p><em>Candida auris</em> is an emerging multidrug-resistant opportunistic fungal pathogen. It</p> <p>poses a significant threat to immunocompromised patients and those with prolonged stays in</p> <p>healthcare facilities. <em>C. auris</em> spreads rapidly in health care facilities through enhanced</p> <p>colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to</p> <p>the virulence, drug resistance, and stress-tolerant nature of <em>C. auris</em> are largely unknown.</p> <p>Current animal models of <em>C. auris</em> infections are not well standardized and report conflicting</p> <p>results. Additional animal models of virulence are needed, especially those amenable to high-</p> <p>throughput analysis. The nematode <em>Caenorhabditis elegans</em> has been validated as an effective</p> <p>tool for studying multiple fungal and bacterial pathogens. In this thesis, I describe a <em>C. elegans</em></p> <p>infection model in which <em>C. auris</em> is lethal to worms with kinetics similar to those observed for</p> <p><em>C. albicans</em>. However, <em>C. auris</em> does not form hyphae, indicating distinct virulence</p> <p>mechanisms. Furthermore, a mutant auxotrophic for adenosine (<em>ade2</em>Δ) is avirulent in this</p> <p>model, demonstrating that the nematode can discriminate between virulent and avirulent</p> <p>strains. The <em>C. elegans</em> model also recapitulates strain-to-strain variability in virulence</p> <p>observed in mouse models. In addition, I have adapted a live/dead staining methodology using</p> <p>SYTOX Orange to enable a high-throughput assay suitable for analyzing multiple strains or</p> <p>genetic mutants. Finally, I used this high-throughput assay to screen an insertion mutant library</p> <p>viifor avirulent mutants and identified several potential novel virulence factors. This model has</p> <p>significant advantages relative to other invertebrate virulence models for <em>C. auris</em> and is a</p> <p>beneficial complement to the more challenging and variable murine models.</p>","abstract_html":"&lt;p&gt;&lt;em&gt;Candida auris&lt;/em&gt; is an emerging multidrug-resistant opportunistic fungal pathogen. It&lt;/p&gt; &lt;p&gt;poses a significant threat to immunocompromised patients and those with prolonged stays in&lt;/p&gt; &lt;p&gt;healthcare facilities. &lt;em&gt;C. auris&lt;/em&gt; spreads rapidly in health care facilities through enhanced&lt;/p&gt; &lt;p&gt;colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to&lt;/p&gt; &lt;p&gt;the virulence, drug resistance, and stress-tolerant nature of &lt;em&gt;C. auris&lt;/em&gt; are largely unknown.&lt;/p&gt; &lt;p&gt;Current animal models of &lt;em&gt;C. auris&lt;/em&gt; infections are not well standardized and report conflicting&lt;/p&gt; &lt;p&gt;results. Additional animal models of virulence are needed, especially those amenable to high-&lt;/p&gt; &lt;p&gt;throughput analysis. The nematode &lt;em&gt;Caenorhabditis elegans&lt;/em&gt; has been validated as an effective&lt;/p&gt; &lt;p&gt;tool for studying multiple fungal and bacterial pathogens. In this thesis, I describe a &lt;em&gt;C. elegans&lt;/em&gt;&lt;/p&gt; &lt;p&gt;infection model in which &lt;em&gt;C. auris&lt;/em&gt; is lethal to worms with kinetics similar to those observed for&lt;/p&gt; &lt;p&gt;&lt;em&gt;C. albicans&lt;/em&gt;. However, &lt;em&gt;C. auris&lt;/em&gt; does not form hyphae, indicating distinct virulence&lt;/p&gt; &lt;p&gt;mechanisms. Furthermore, a mutant auxotrophic for adenosine (&lt;em&gt;ade2&lt;/em&gt;Δ) is avirulent in this&lt;/p&gt; &lt;p&gt;model, demonstrating that the nematode can discriminate between virulent and avirulent&lt;/p&gt; &lt;p&gt;strains. The &lt;em&gt;C. elegans&lt;/em&gt; model also recapitulates strain-to-strain variability in virulence&lt;/p&gt; &lt;p&gt;observed in mouse models. In addition, I have adapted a live/dead staining methodology using&lt;/p&gt; &lt;p&gt;SYTOX Orange to enable a high-throughput assay suitable for analyzing multiple strains or&lt;/p&gt; &lt;p&gt;genetic mutants. Finally, I used this high-throughput assay to screen an insertion mutant library&lt;/p&gt; &lt;p&gt;viifor avirulent mutants and identified several potential novel virulence factors. This model has&lt;/p&gt; &lt;p&gt;significant advantages relative to other invertebrate virulence models for &lt;em&gt;C. auris&lt;/em&gt; and is a&lt;/p&gt; &lt;p&gt;beneficial complement to the more challenging and variable murine models.&lt;/p&gt;","abstract_has_math":false,"creators":["Martinez, Melissa","<p>https://orcid.org/0000-0002-0359-7362</p>"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Michael Lorenz, PhD","Danielle Garsin, PhD","Theresa M. Koehler, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2026,"date_issued":"2026-05-01T07:00:00Z","date_published":"2026-05-01T07:00:00Z","updated_at":"2026-07-24T05:50:47Z","subjects":["Candida auris","Candidozyma auris","Caenorhabditis elegans","Animal Model","Animal Experimentation and Research","Microbiology","Pathogenic Microbiology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1506","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Michael Lorenz, PhD","Danielle Garsin, PhD","Theresa M. 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It</p> <p>poses a significant threat to immunocompromised patients and those with prolonged stays in</p> <p>healthcare facilities. <em>C. auris</em> spreads rapidly in health care facilities through enhanced</p> <p>colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to</p> <p>the virulence, drug resistance, and stress-tolerant nature of <em>C. auris</em> are largely unknown.</p> <p>Current animal models of <em>C. auris</em> infections are not well standardized and report conflicting</p> <p>results. Additional animal models of virulence are needed, especially those amenable to high-</p> <p>throughput analysis. The nematode <em>Caenorhabditis elegans</em> has been validated as an effective</p> <p>tool for studying multiple fungal and bacterial pathogens. In this thesis, I describe a <em>C. elegans</em></p> <p>infection model in which <em>C. auris</em> is lethal to worms with kinetics similar to those observed for</p> <p><em>C. albicans</em>. However, <em>C. auris</em> does not form hyphae, indicating distinct virulence</p> <p>mechanisms. Furthermore, a mutant auxotrophic for adenosine (<em>ade2</em>Δ) is avirulent in this</p> <p>model, demonstrating that the nematode can discriminate between virulent and avirulent</p> <p>strains. The <em>C. elegans</em> model also recapitulates strain-to-strain variability in virulence</p> <p>observed in mouse models. In addition, I have adapted a live/dead staining methodology using</p> <p>SYTOX Orange to enable a high-throughput assay suitable for analyzing multiple strains or</p> <p>genetic mutants. Finally, I used this high-throughput assay to screen an insertion mutant library</p> <p>viifor avirulent mutants and identified several potential novel virulence factors. This model has</p> <p>significant advantages relative to other invertebrate virulence models for <em>C. auris</em> and is a</p> <p>beneficial complement to the more challenging and variable murine models.</p>"]},{"key":"dc:title","label":"Title","values":["A tractable nematode model for the emerging fungal pathogen, Candida auris"]}]}],"canonical_facts":{"dc:contributor":["Michael Lorenz, PhD","Danielle Garsin, PhD","Theresa M. Koehler, PhD"],"dc:creator":["Martinez, Melissa","<p>https://orcid.org/0000-0002-0359-7362</p>"],"dc:date.available":["2026-02-24T08:00:00Z"],"dc:description.abstract":["<p><em>Candida auris</em> is an emerging multidrug-resistant opportunistic fungal pathogen. It</p> <p>poses a significant threat to immunocompromised patients and those with prolonged stays in</p> <p>healthcare facilities. <em>C. auris</em> spreads rapidly in health care facilities through enhanced</p> <p>colonization of skin and abiotic surfaces. The genetic factors contributing to this ability and to</p> <p>the virulence, drug resistance, and stress-tolerant nature of <em>C. auris</em> are largely unknown.</p> <p>Current animal models of <em>C. auris</em> infections are not well standardized and report conflicting</p> <p>results. Additional animal models of virulence are needed, especially those amenable to high-</p> <p>throughput analysis. The nematode <em>Caenorhabditis elegans</em> has been validated as an effective</p> <p>tool for studying multiple fungal and bacterial pathogens. In this thesis, I describe a <em>C. elegans</em></p> <p>infection model in which <em>C. auris</em> is lethal to worms with kinetics similar to those observed for</p> <p><em>C. albicans</em>. However, <em>C. auris</em> does not form hyphae, indicating distinct virulence</p> <p>mechanisms. Furthermore, a mutant auxotrophic for adenosine (<em>ade2</em>Δ) is avirulent in this</p> <p>model, demonstrating that the nematode can discriminate between virulent and avirulent</p> <p>strains. The <em>C. elegans</em> model also recapitulates strain-to-strain variability in virulence</p> <p>observed in mouse models. In addition, I have adapted a live/dead staining methodology using</p> <p>SYTOX Orange to enable a high-throughput assay suitable for analyzing multiple strains or</p> <p>genetic mutants. Finally, I used this high-throughput assay to screen an insertion mutant library</p> <p>viifor avirulent mutants and identified several potential novel virulence factors. This model has</p> <p>significant advantages relative to other invertebrate virulence models for <em>C. auris</em> and is a</p> <p>beneficial complement to the more challenging and variable murine models.</p>"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/1506"],"dc:subject":["Candida auris","Candidozyma auris","Caenorhabditis elegans","Animal Model","Animal Experimentation and Research","Microbiology","Pathogenic Microbiology"],"dc:title":["A tractable nematode model for the emerging fungal pathogen, Candida auris"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:47Z"}