Biochemical Analysis of Caur SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris
is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat . Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of...
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| Veröffentlicht in: | ACS infectious diseases 2022-03, Vol.8 (3), p.584-595 |
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| creator | Chandler, Courtney E Hernandez, Francisco G Totten, Marissa Robinett, Natalie G Schatzman, Sabrina S Zhang, Sean X Culotta, Valeria C |
| description | is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat
. Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of host immunity. Cu-only SODs are essential for the virulence of diverse fungal pathogens; however, little is understood about these enzymes in
We show here that
secretes an enzymatically active Cu-only SOD (
SOD4) when cells are starved for Fe, a condition mimicking host environments. Although predicted to attach to cell walls,
SOD4 is detected as a soluble extracellular enzyme and can act at a distance to remove superoxide.
SOD4 selectively binds Cu and not Zn, and Cu binding is labile compared to bimetallic Cu/Zn SODs. Moreover,
SOD4 is susceptible to inhibition by various metal-binding drugs that are without effect on mammalian Cu/Zn SODs. Our studies highlight
SOD4 as a potential antifungal target worthy of consideration. |
| doi_str_mv | 10.1021/acsinfecdis.1c00590 |
| format | Article |
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. Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of host immunity. Cu-only SODs are essential for the virulence of diverse fungal pathogens; however, little is understood about these enzymes in
We show here that
secretes an enzymatically active Cu-only SOD (
SOD4) when cells are starved for Fe, a condition mimicking host environments. Although predicted to attach to cell walls,
SOD4 is detected as a soluble extracellular enzyme and can act at a distance to remove superoxide.
SOD4 selectively binds Cu and not Zn, and Cu binding is labile compared to bimetallic Cu/Zn SODs. Moreover,
SOD4 is susceptible to inhibition by various metal-binding drugs that are without effect on mammalian Cu/Zn SODs. Our studies highlight
SOD4 as a potential antifungal target worthy of consideration.</description><identifier>ISSN: 2373-8227</identifier><identifier>EISSN: 2373-8227</identifier><identifier>DOI: 10.1021/acsinfecdis.1c00590</identifier><identifier>PMID: 35179882</identifier><language>eng</language><publisher>United States</publisher><subject>Animals ; Antifungal Agents - pharmacology ; Candida auris - drug effects ; Candida auris - enzymology ; Candida auris - metabolism ; Candida auris - pathogenicity ; Copper - metabolism ; Drug Resistance, Multiple, Fungal - drug effects ; Drug Resistance, Multiple, Fungal - physiology ; Mammals - metabolism ; Superoxide Dismutase - metabolism ; Virulence - physiology ; Zinc - metabolism</subject><ispartof>ACS infectious diseases, 2022-03, Vol.8 (3), p.584-595</ispartof><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c672-e7589b2214eaf51c4f8d65627e2034d74ef38bfb77795f6d698a6c37f42e81d83</cites><orcidid>0000-0002-3213-1326</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,2765,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35179882$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chandler, Courtney E</creatorcontrib><creatorcontrib>Hernandez, Francisco G</creatorcontrib><creatorcontrib>Totten, Marissa</creatorcontrib><creatorcontrib>Robinett, Natalie G</creatorcontrib><creatorcontrib>Schatzman, Sabrina S</creatorcontrib><creatorcontrib>Zhang, Sean X</creatorcontrib><creatorcontrib>Culotta, Valeria C</creatorcontrib><title>Biochemical Analysis of Caur SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris</title><title>ACS infectious diseases</title><addtitle>ACS Infect Dis</addtitle><description>is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat
. Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of host immunity. Cu-only SODs are essential for the virulence of diverse fungal pathogens; however, little is understood about these enzymes in
We show here that
secretes an enzymatically active Cu-only SOD (
SOD4) when cells are starved for Fe, a condition mimicking host environments. Although predicted to attach to cell walls,
SOD4 is detected as a soluble extracellular enzyme and can act at a distance to remove superoxide.
SOD4 selectively binds Cu and not Zn, and Cu binding is labile compared to bimetallic Cu/Zn SODs. Moreover,
SOD4 is susceptible to inhibition by various metal-binding drugs that are without effect on mammalian Cu/Zn SODs. Our studies highlight
SOD4 as a potential antifungal target worthy of consideration.</description><subject>Animals</subject><subject>Antifungal Agents - pharmacology</subject><subject>Candida auris - drug effects</subject><subject>Candida auris - enzymology</subject><subject>Candida auris - metabolism</subject><subject>Candida auris - pathogenicity</subject><subject>Copper - metabolism</subject><subject>Drug Resistance, Multiple, Fungal - drug effects</subject><subject>Drug Resistance, Multiple, Fungal - physiology</subject><subject>Mammals - metabolism</subject><subject>Superoxide Dismutase - metabolism</subject><subject>Virulence - physiology</subject><subject>Zinc - metabolism</subject><issn>2373-8227</issn><issn>2373-8227</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkF9PwjAURxujEYJ8AhPTD-Cwf7a1e0QENSGBxL0vXXu71cC2tNsD394Z0PB078PvnIeD0CMlC0oYfVE6uMaCNi4sqCYkycgNmjIueCQZE7dX_wTNQ_gmhFAukzhO7tGEJ1RkUrIp6l5dq2s4Oq0OeNmowym4gFuLV2rw-Gv3Fj9jhfdtD03vxkleg1cdDL3TOFe-gh7b1uO-Brw-gq9cU-HN0FTjdK_6uq2gGVWNcUbh0ejCA7qz6hBgfrkzlG_W-eoj2u7eP1fLbaRTwSIQicxKxmgMyiZUx1aaNEmZAEZ4bEQMlsvSlkKILLGpSTOpUs2FjRlIaiSfIX7Wat-G4MEWnXdH5U8FJcVvweKqYHEpOFJPZ6obyiOYf-avF_8BLg5vsQ</recordid><startdate>20220311</startdate><enddate>20220311</enddate><creator>Chandler, Courtney E</creator><creator>Hernandez, Francisco G</creator><creator>Totten, Marissa</creator><creator>Robinett, Natalie G</creator><creator>Schatzman, Sabrina S</creator><creator>Zhang, Sean X</creator><creator>Culotta, Valeria C</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-3213-1326</orcidid></search><sort><creationdate>20220311</creationdate><title>Biochemical Analysis of Caur SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris</title><author>Chandler, Courtney E ; Hernandez, Francisco G ; Totten, Marissa ; Robinett, Natalie G ; Schatzman, Sabrina S ; Zhang, Sean X ; Culotta, Valeria C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c672-e7589b2214eaf51c4f8d65627e2034d74ef38bfb77795f6d698a6c37f42e81d83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Antifungal Agents - pharmacology</topic><topic>Candida auris - drug effects</topic><topic>Candida auris - enzymology</topic><topic>Candida auris - metabolism</topic><topic>Candida auris - pathogenicity</topic><topic>Copper - metabolism</topic><topic>Drug Resistance, Multiple, Fungal - drug effects</topic><topic>Drug Resistance, Multiple, Fungal - physiology</topic><topic>Mammals - metabolism</topic><topic>Superoxide Dismutase - metabolism</topic><topic>Virulence - physiology</topic><topic>Zinc - metabolism</topic><toplevel>online_resources</toplevel><creatorcontrib>Chandler, Courtney E</creatorcontrib><creatorcontrib>Hernandez, Francisco G</creatorcontrib><creatorcontrib>Totten, Marissa</creatorcontrib><creatorcontrib>Robinett, Natalie G</creatorcontrib><creatorcontrib>Schatzman, Sabrina S</creatorcontrib><creatorcontrib>Zhang, Sean X</creatorcontrib><creatorcontrib>Culotta, Valeria C</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>ACS infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chandler, Courtney E</au><au>Hernandez, Francisco G</au><au>Totten, Marissa</au><au>Robinett, Natalie G</au><au>Schatzman, Sabrina S</au><au>Zhang, Sean X</au><au>Culotta, Valeria C</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biochemical Analysis of Caur SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris</atitle><jtitle>ACS infectious diseases</jtitle><addtitle>ACS Infect Dis</addtitle><date>2022-03-11</date><risdate>2022</risdate><volume>8</volume><issue>3</issue><spage>584</spage><epage>595</epage><pages>584-595</pages><issn>2373-8227</issn><eissn>2373-8227</eissn><abstract>is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat
. Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of host immunity. Cu-only SODs are essential for the virulence of diverse fungal pathogens; however, little is understood about these enzymes in
We show here that
secretes an enzymatically active Cu-only SOD (
SOD4) when cells are starved for Fe, a condition mimicking host environments. Although predicted to attach to cell walls,
SOD4 is detected as a soluble extracellular enzyme and can act at a distance to remove superoxide.
SOD4 selectively binds Cu and not Zn, and Cu binding is labile compared to bimetallic Cu/Zn SODs. Moreover,
SOD4 is susceptible to inhibition by various metal-binding drugs that are without effect on mammalian Cu/Zn SODs. Our studies highlight
SOD4 as a potential antifungal target worthy of consideration.</abstract><cop>United States</cop><pmid>35179882</pmid><doi>10.1021/acsinfecdis.1c00590</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-3213-1326</orcidid></addata></record> |
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| source | MEDLINE; ACS Publications |
| subjects | Animals Antifungal Agents - pharmacology Candida auris - drug effects Candida auris - enzymology Candida auris - metabolism Candida auris - pathogenicity Copper - metabolism Drug Resistance, Multiple, Fungal - drug effects Drug Resistance, Multiple, Fungal - physiology Mammals - metabolism Superoxide Dismutase - metabolism Virulence - physiology Zinc - metabolism |
| title | Biochemical Analysis of Caur SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen Candida auris |
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