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Rapid Detection of ERG11 -Associated Azole Resistance and FKS -Associated Echinocandin Resistance in Candida auris
is an emerging multidrug-resistant yeast that can cause serious invasive infections. The accurate and rapid assessment of antifungal resistance is important for effective patient management. A novel and highly accurate diagnostic platform was established for the rapid identification of mutations con...
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| Published in: | Antimicrobial agents and chemotherapy 2019-01, Vol.63 (1) |
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| container_title | Antimicrobial agents and chemotherapy |
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| creator | Hou, Xin Lee, Annie Jiménez-Ortigosa, Cristina Kordalewska, Milena Perlin, David S Zhao, Yanan |
| description | is an emerging multidrug-resistant yeast that can cause serious invasive infections. The accurate and rapid assessment of antifungal resistance is important for effective patient management. A novel and highly accurate diagnostic platform was established for the rapid identification of
mutations conferring azole resistance and
mutations associated with echinocandin resistance in
Using allele-specific molecular beacons and DNA melting curve analysis following asymmetric PCR, a duplex
assay and a simplex
HS1 assay were developed to identify the most prominent resistance-associated mutations (Y132F and K143R in
; S639F in
HS1) within 2 h. Assays were validated by testing a panel of 94
clinical isolates in a blind manner. The molecular diagnostic results from the assays were 100% concordant with DNA sequencing results. This platform has the potential to overcome the deficiencies of existing
susceptibility-based assays to identify azole- and/or echinocandin-resistant
, and thus, it holds promise as a surrogate diagnostic method to direct antifungal therapy more effectively. |
| doi_str_mv | 10.1128/AAC.01811-18 |
| format | article |
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mutations conferring azole resistance and
mutations associated with echinocandin resistance in
Using allele-specific molecular beacons and DNA melting curve analysis following asymmetric PCR, a duplex
assay and a simplex
HS1 assay were developed to identify the most prominent resistance-associated mutations (Y132F and K143R in
; S639F in
HS1) within 2 h. Assays were validated by testing a panel of 94
clinical isolates in a blind manner. The molecular diagnostic results from the assays were 100% concordant with DNA sequencing results. This platform has the potential to overcome the deficiencies of existing
susceptibility-based assays to identify azole- and/or echinocandin-resistant
, and thus, it holds promise as a surrogate diagnostic method to direct antifungal therapy more effectively.</description><identifier>ISSN: 0066-4804</identifier><identifier>EISSN: 1098-6596</identifier><identifier>DOI: 10.1128/AAC.01811-18</identifier><identifier>PMID: 30397051</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Amino Acid Substitution ; Anidulafungin - pharmacology ; Antifungal Agents ; Antifungal Agents - pharmacology ; Candida ; Candida - drug effects ; Candida - enzymology ; Candida - genetics ; Candida - isolation & purification ; Candidiasis - drug therapy ; Candidiasis - microbiology ; Caspofungin - pharmacology ; Cytochrome P-450 Enzyme System ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; DNA Mutational Analysis ; Drug Resistance, Fungal ; Drug Resistance, Fungal - genetics ; Fluconazole - pharmacology ; Fungal Proteins ; Fungal Proteins - genetics ; Fungal Proteins - metabolism ; Gene Expression ; Glucosyltransferases ; Glucosyltransferases - genetics ; Glucosyltransferases - metabolism ; Humans ; Mechanisms of Resistance ; Micafungin - pharmacology ; Mutation ; Nucleic Acid Denaturation ; Polymerase Chain Reaction ; Polymerase Chain Reaction - methods ; Voriconazole - pharmacology</subject><ispartof>Antimicrobial agents and chemotherapy, 2019-01, Vol.63 (1)</ispartof><rights>Copyright © 2018 American Society for Microbiology.</rights><rights>Copyright © 2018 American Society for Microbiology. 2018 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a418t-fe0219a45783fdaa4396ddcbc200425860edc867894a5e087da56bae894834313</citedby><cites>FETCH-LOGICAL-a418t-fe0219a45783fdaa4396ddcbc200425860edc867894a5e087da56bae894834313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.asm.org/doi/pdf/10.1128/AAC.01811-18$$EPDF$$P50$$Gasm2$$H</linktopdf><linktohtml>$$Uhttps://journals.asm.org/doi/full/10.1128/AAC.01811-18$$EHTML$$P50$$Gasm2$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,3188,27924,27925,52751,52752,52753,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30397051$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hou, Xin</creatorcontrib><creatorcontrib>Lee, Annie</creatorcontrib><creatorcontrib>Jiménez-Ortigosa, Cristina</creatorcontrib><creatorcontrib>Kordalewska, Milena</creatorcontrib><creatorcontrib>Perlin, David S</creatorcontrib><creatorcontrib>Zhao, Yanan</creatorcontrib><title>Rapid Detection of ERG11 -Associated Azole Resistance and FKS -Associated Echinocandin Resistance in Candida auris</title><title>Antimicrobial agents and chemotherapy</title><addtitle>Antimicrob Agents Chemother</addtitle><addtitle>Antimicrob Agents Chemother</addtitle><description>is an emerging multidrug-resistant yeast that can cause serious invasive infections. The accurate and rapid assessment of antifungal resistance is important for effective patient management. A novel and highly accurate diagnostic platform was established for the rapid identification of
mutations conferring azole resistance and
mutations associated with echinocandin resistance in
Using allele-specific molecular beacons and DNA melting curve analysis following asymmetric PCR, a duplex
assay and a simplex
HS1 assay were developed to identify the most prominent resistance-associated mutations (Y132F and K143R in
; S639F in
HS1) within 2 h. Assays were validated by testing a panel of 94
clinical isolates in a blind manner. The molecular diagnostic results from the assays were 100% concordant with DNA sequencing results. This platform has the potential to overcome the deficiencies of existing
susceptibility-based assays to identify azole- and/or echinocandin-resistant
, and thus, it holds promise as a surrogate diagnostic method to direct antifungal therapy more effectively.</description><subject>Amino Acid Substitution</subject><subject>Anidulafungin - pharmacology</subject><subject>Antifungal Agents</subject><subject>Antifungal Agents - pharmacology</subject><subject>Candida</subject><subject>Candida - drug effects</subject><subject>Candida - enzymology</subject><subject>Candida - genetics</subject><subject>Candida - isolation & purification</subject><subject>Candidiasis - drug therapy</subject><subject>Candidiasis - microbiology</subject><subject>Caspofungin - pharmacology</subject><subject>Cytochrome P-450 Enzyme System</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>DNA Mutational Analysis</subject><subject>Drug Resistance, Fungal</subject><subject>Drug Resistance, Fungal - genetics</subject><subject>Fluconazole - pharmacology</subject><subject>Fungal Proteins</subject><subject>Fungal Proteins - genetics</subject><subject>Fungal Proteins - metabolism</subject><subject>Gene Expression</subject><subject>Glucosyltransferases</subject><subject>Glucosyltransferases - genetics</subject><subject>Glucosyltransferases - metabolism</subject><subject>Humans</subject><subject>Mechanisms of Resistance</subject><subject>Micafungin - pharmacology</subject><subject>Mutation</subject><subject>Nucleic Acid Denaturation</subject><subject>Polymerase Chain Reaction</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Voriconazole - pharmacology</subject><issn>0066-4804</issn><issn>1098-6596</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp1kdFrFDEQxoMo9lp981nyaMGtk2STy74Iy3mtYkE49TnMJVmbspecya6gf71pr5b2wafhm_nxDTMfIa8YnDHG9bu-X50B04w1TD8hCwadbpTs1FOyAFCqaTW0R-S4lGuoWnbwnBwJEN0SJFuQvMF9cPSDn7ydQoo0DXS9uWCMNn0pyQacvKP9nzR6uvEllAmj9RSjo-efvz6C1vYqxGTrKMSHbFWrm6ZDinMO5QV5NuBY_Mu7ekK-n6-_rT42l18uPq36ywZbpqdm8MBZh61cajE4xFZ0yjm7tRyg5VIr8M5qtdRdi9KDXjqUaou-ai1awcQJeX_w3c_bXWV9nDKOZp_DDvNvkzCYx5MYrsyP9MsowSXnvBq8uTPI6efsy2R2oVg_jhh9movhrP4RpJKiom8PqM2plOyH-zUMzE1MpsZkbmMyTFf89IBj2XFzneYc6yf-x75-eMa98b8MxV9uQZml</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Hou, Xin</creator><creator>Lee, Annie</creator><creator>Jiménez-Ortigosa, Cristina</creator><creator>Kordalewska, Milena</creator><creator>Perlin, David S</creator><creator>Zhao, Yanan</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190101</creationdate><title>Rapid Detection of ERG11 -Associated Azole Resistance and FKS -Associated Echinocandin Resistance in Candida auris</title><author>Hou, Xin ; Lee, Annie ; Jiménez-Ortigosa, Cristina ; Kordalewska, Milena ; Perlin, David S ; Zhao, Yanan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a418t-fe0219a45783fdaa4396ddcbc200425860edc867894a5e087da56bae894834313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Amino Acid Substitution</topic><topic>Anidulafungin - pharmacology</topic><topic>Antifungal Agents</topic><topic>Antifungal Agents - pharmacology</topic><topic>Candida</topic><topic>Candida - drug effects</topic><topic>Candida - enzymology</topic><topic>Candida - genetics</topic><topic>Candida - isolation & purification</topic><topic>Candidiasis - drug therapy</topic><topic>Candidiasis - microbiology</topic><topic>Caspofungin - pharmacology</topic><topic>Cytochrome P-450 Enzyme System</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>DNA Mutational Analysis</topic><topic>Drug Resistance, Fungal</topic><topic>Drug Resistance, Fungal - genetics</topic><topic>Fluconazole - pharmacology</topic><topic>Fungal Proteins</topic><topic>Fungal Proteins - genetics</topic><topic>Fungal Proteins - metabolism</topic><topic>Gene Expression</topic><topic>Glucosyltransferases</topic><topic>Glucosyltransferases - genetics</topic><topic>Glucosyltransferases - metabolism</topic><topic>Humans</topic><topic>Mechanisms of Resistance</topic><topic>Micafungin - pharmacology</topic><topic>Mutation</topic><topic>Nucleic Acid Denaturation</topic><topic>Polymerase Chain Reaction</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Voriconazole - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hou, Xin</creatorcontrib><creatorcontrib>Lee, Annie</creatorcontrib><creatorcontrib>Jiménez-Ortigosa, Cristina</creatorcontrib><creatorcontrib>Kordalewska, Milena</creatorcontrib><creatorcontrib>Perlin, David S</creatorcontrib><creatorcontrib>Zhao, Yanan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Antimicrobial agents and chemotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hou, Xin</au><au>Lee, Annie</au><au>Jiménez-Ortigosa, Cristina</au><au>Kordalewska, Milena</au><au>Perlin, David S</au><au>Zhao, Yanan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapid Detection of ERG11 -Associated Azole Resistance and FKS -Associated Echinocandin Resistance in Candida auris</atitle><jtitle>Antimicrobial agents and chemotherapy</jtitle><stitle>Antimicrob Agents Chemother</stitle><addtitle>Antimicrob Agents Chemother</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>63</volume><issue>1</issue><issn>0066-4804</issn><eissn>1098-6596</eissn><abstract>is an emerging multidrug-resistant yeast that can cause serious invasive infections. The accurate and rapid assessment of antifungal resistance is important for effective patient management. A novel and highly accurate diagnostic platform was established for the rapid identification of
mutations conferring azole resistance and
mutations associated with echinocandin resistance in
Using allele-specific molecular beacons and DNA melting curve analysis following asymmetric PCR, a duplex
assay and a simplex
HS1 assay were developed to identify the most prominent resistance-associated mutations (Y132F and K143R in
; S639F in
HS1) within 2 h. Assays were validated by testing a panel of 94
clinical isolates in a blind manner. The molecular diagnostic results from the assays were 100% concordant with DNA sequencing results. This platform has the potential to overcome the deficiencies of existing
susceptibility-based assays to identify azole- and/or echinocandin-resistant
, and thus, it holds promise as a surrogate diagnostic method to direct antifungal therapy more effectively.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>30397051</pmid><doi>10.1128/AAC.01811-18</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Antimicrobial agents and chemotherapy, 2019-01, Vol.63 (1) |
| issn | 0066-4804 1098-6596 |
| language | eng |
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| source | American Society for Microbiology Journals; PubMed Central |
| subjects | Amino Acid Substitution Anidulafungin - pharmacology Antifungal Agents Antifungal Agents - pharmacology Candida Candida - drug effects Candida - enzymology Candida - genetics Candida - isolation & purification Candidiasis - drug therapy Candidiasis - microbiology Caspofungin - pharmacology Cytochrome P-450 Enzyme System Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism DNA Mutational Analysis Drug Resistance, Fungal Drug Resistance, Fungal - genetics Fluconazole - pharmacology Fungal Proteins Fungal Proteins - genetics Fungal Proteins - metabolism Gene Expression Glucosyltransferases Glucosyltransferases - genetics Glucosyltransferases - metabolism Humans Mechanisms of Resistance Micafungin - pharmacology Mutation Nucleic Acid Denaturation Polymerase Chain Reaction Polymerase Chain Reaction - methods Voriconazole - pharmacology |
| title | Rapid Detection of ERG11 -Associated Azole Resistance and FKS -Associated Echinocandin Resistance in Candida auris |
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