A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis
Drug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmiss...
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| Veröffentlicht in: | Scientific reports 2019-03, Vol.9 (1), p.4425-4425, Article 4425 |
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| creator | Chen, Ching-Yu Weng, Jui-Yun Huang, Hsin-Hui Yen, Wen-Chun Tsai, Yu-Han Cheng, Tsung Chain Jou, Ruwen |
| description | Drug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmission associated-mutations of
Mycobacterium tuberculosis
complex (MTBC) isolates in 6 to 7 hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes:
rpoB
,
katG
,
inhA
,
ahpC
,
embB
,
rpsL
,
gyrA
,
rrs
and
eis
. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDR
plus
and MTBDR
sl
tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDR
plus
test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDR
sl
test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations. |
| doi_str_mv | 10.1038/s41598-019-39339-3 |
| format | Article |
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Mycobacterium tuberculosis
complex (MTBC) isolates in 6 to 7 hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes:
rpoB
,
katG
,
inhA
,
ahpC
,
embB
,
rpsL
,
gyrA
,
rrs
and
eis
. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDR
plus
and MTBDR
sl
tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDR
plus
test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDR
sl
test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-39339-3</identifier><identifier>PMID: 30872613</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45 ; 45/23 ; 45/61 ; 45/77 ; 631/61/32 ; 692/699/255/1856 ; Antitubercular Agents - therapeutic use ; Bacterial Proteins - genetics ; Discordance ; DNA microarrays ; DNA, Bacterial - analysis ; DNA, Bacterial - genetics ; Drug resistance ; Drug Resistance, Multiple, Bacterial - genetics ; Epidemiology ; Ethambutol ; Extensively Drug-Resistant Tuberculosis - drug therapy ; Extensively Drug-Resistant Tuberculosis - microbiology ; Fluoroquinolones ; Genotype ; Humanities and Social Sciences ; Humans ; Isoniazid ; Microbial Sensitivity Tests ; multidisciplinary ; Multidrug resistance ; Mutation ; Mycobacterium tuberculosis - classification ; Mycobacterium tuberculosis - drug effects ; Mycobacterium tuberculosis - genetics ; Mycobacterium tuberculosis - isolation & purification ; Oligonucleotide Array Sequence Analysis - methods ; Oligonucleotides ; Primers ; Rifampin ; RpoB protein ; Science ; Science (multidisciplinary) ; Sequence Analysis, DNA - methods ; Single-nucleotide polymorphism ; Streptomycin ; Tuberculosis</subject><ispartof>Scientific reports, 2019-03, Vol.9 (1), p.4425-4425, Article 4425</ispartof><rights>The Author(s) 2019</rights><rights>This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c511t-601e32441e4ea9b91efeaf06e4554716cc4a06284cb13a0afcbd8121c620f7c63</citedby><cites>FETCH-LOGICAL-c511t-601e32441e4ea9b91efeaf06e4554716cc4a06284cb13a0afcbd8121c620f7c63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418274/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418274/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30872613$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Ching-Yu</creatorcontrib><creatorcontrib>Weng, Jui-Yun</creatorcontrib><creatorcontrib>Huang, Hsin-Hui</creatorcontrib><creatorcontrib>Yen, Wen-Chun</creatorcontrib><creatorcontrib>Tsai, Yu-Han</creatorcontrib><creatorcontrib>Cheng, Tsung Chain</creatorcontrib><creatorcontrib>Jou, Ruwen</creatorcontrib><title>A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Drug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmission associated-mutations of
Mycobacterium tuberculosis
complex (MTBC) isolates in 6 to 7 hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes:
rpoB
,
katG
,
inhA
,
ahpC
,
embB
,
rpsL
,
gyrA
,
rrs
and
eis
. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDR
plus
and MTBDR
sl
tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDR
plus
test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDR
sl
test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations.</description><subject>45</subject><subject>45/23</subject><subject>45/61</subject><subject>45/77</subject><subject>631/61/32</subject><subject>692/699/255/1856</subject><subject>Antitubercular Agents - therapeutic use</subject><subject>Bacterial Proteins - genetics</subject><subject>Discordance</subject><subject>DNA microarrays</subject><subject>DNA, Bacterial - analysis</subject><subject>DNA, Bacterial - genetics</subject><subject>Drug resistance</subject><subject>Drug Resistance, Multiple, Bacterial - genetics</subject><subject>Epidemiology</subject><subject>Ethambutol</subject><subject>Extensively Drug-Resistant Tuberculosis - drug therapy</subject><subject>Extensively Drug-Resistant Tuberculosis - microbiology</subject><subject>Fluoroquinolones</subject><subject>Genotype</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Isoniazid</subject><subject>Microbial Sensitivity Tests</subject><subject>multidisciplinary</subject><subject>Multidrug resistance</subject><subject>Mutation</subject><subject>Mycobacterium tuberculosis - classification</subject><subject>Mycobacterium tuberculosis - drug effects</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - isolation & purification</subject><subject>Oligonucleotide Array Sequence Analysis - methods</subject><subject>Oligonucleotides</subject><subject>Primers</subject><subject>Rifampin</subject><subject>RpoB protein</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sequence Analysis, DNA - methods</subject><subject>Single-nucleotide polymorphism</subject><subject>Streptomycin</subject><subject>Tuberculosis</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc9vFSEQx4nR2Kb2H_BgSLx42coAy1suJk3jjyZNvOiZsOzsloYHFdjq--_l-WqtHuQAk5nPfJnJl5CXwM6AieFtkdDroWOgO6GFaPcTcsyZ7DsuOH_6KD4ip6XcsHZ6riXo5-RIsGHDFYhjspzTiN9pCn5JcXUBU_UTUpuz3dE5ZVqvkU5Y0VWfIk0z3a6hIXldqI0TxR8VY_F3GHZ0n-wyFl-qjQ5pXUfMbg2pZV6QZ7MNBU_v3xPy9cP7LxefuqvPHy8vzq861wPUTjFAwaUElGj1qAFntDNTKPtebkA5Jy1TfJBuBGGZnd04DcDBKc7mjVPihLw76N6u4xYnh7FmG8xt9lubdyZZb_6uRH9tlnRnlISBb2QTeHMvkNO3FUs1W18chmAjprUYDlqA6vmgG_r6H_QmrTm29fYUiB4U7CfiB8rlVErG-WEYYGZvpTlYaZqV5peVRrSmV4_XeGj5bVwDxAEorRQXzH_-_o_sT-lUq_0</recordid><startdate>20190314</startdate><enddate>20190314</enddate><creator>Chen, Ching-Yu</creator><creator>Weng, Jui-Yun</creator><creator>Huang, Hsin-Hui</creator><creator>Yen, Wen-Chun</creator><creator>Tsai, Yu-Han</creator><creator>Cheng, Tsung Chain</creator><creator>Jou, Ruwen</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190314</creationdate><title>A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis</title><author>Chen, Ching-Yu ; Weng, Jui-Yun ; Huang, Hsin-Hui ; Yen, Wen-Chun ; Tsai, Yu-Han ; Cheng, Tsung Chain ; Jou, Ruwen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c511t-601e32441e4ea9b91efeaf06e4554716cc4a06284cb13a0afcbd8121c620f7c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>45</topic><topic>45/23</topic><topic>45/61</topic><topic>45/77</topic><topic>631/61/32</topic><topic>692/699/255/1856</topic><topic>Antitubercular Agents - therapeutic use</topic><topic>Bacterial Proteins - genetics</topic><topic>Discordance</topic><topic>DNA microarrays</topic><topic>DNA, Bacterial - analysis</topic><topic>DNA, Bacterial - genetics</topic><topic>Drug resistance</topic><topic>Drug Resistance, Multiple, Bacterial - genetics</topic><topic>Epidemiology</topic><topic>Ethambutol</topic><topic>Extensively Drug-Resistant Tuberculosis - drug therapy</topic><topic>Extensively Drug-Resistant Tuberculosis - microbiology</topic><topic>Fluoroquinolones</topic><topic>Genotype</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Isoniazid</topic><topic>Microbial Sensitivity Tests</topic><topic>multidisciplinary</topic><topic>Multidrug resistance</topic><topic>Mutation</topic><topic>Mycobacterium tuberculosis - classification</topic><topic>Mycobacterium tuberculosis - drug effects</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - isolation & purification</topic><topic>Oligonucleotide Array Sequence Analysis - methods</topic><topic>Oligonucleotides</topic><topic>Primers</topic><topic>Rifampin</topic><topic>RpoB protein</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Sequence Analysis, DNA - methods</topic><topic>Single-nucleotide polymorphism</topic><topic>Streptomycin</topic><topic>Tuberculosis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Ching-Yu</creatorcontrib><creatorcontrib>Weng, Jui-Yun</creatorcontrib><creatorcontrib>Huang, Hsin-Hui</creatorcontrib><creatorcontrib>Yen, Wen-Chun</creatorcontrib><creatorcontrib>Tsai, Yu-Han</creatorcontrib><creatorcontrib>Cheng, Tsung Chain</creatorcontrib><creatorcontrib>Jou, Ruwen</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Ching-Yu</au><au>Weng, Jui-Yun</au><au>Huang, Hsin-Hui</au><au>Yen, Wen-Chun</au><au>Tsai, Yu-Han</au><au>Cheng, Tsung Chain</au><au>Jou, Ruwen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-03-14</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>4425</spage><epage>4425</epage><pages>4425-4425</pages><artnum>4425</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Drug-resistant tuberculosis (TB) is a global crisis and a threat to health security. Since conventional drug susceptibility testing (DST) takes several weeks, we herein described a molecular assay to rapidly identify multidrug-resistant (MDR) and extensively drug-resistant (XDR) and reveal transmission associated-mutations of
Mycobacterium tuberculosis
complex (MTBC) isolates in 6 to 7 hours. An array was designed with 12 pairs of primers and 60 single nucleotide polymorphisms of 9 genes:
rpoB
,
katG
,
inhA
,
ahpC
,
embB
,
rpsL
,
gyrA
,
rrs
and
eis
. We assessed the performance of the array using 176 clinical MTBC isolates. The results of culture-based DST were used as the gold standard, the GenoType MTBDR
plus
and MTBDR
sl
tests were used for parallel comparison, and gene sequencing was performed to resolve the discordance. The sensitivities and specificities of the array are comparable to those of the MTBDR
plus
test for resistance to isoniazid (INH) (100.0%, 96.7%) and rifampicin (RIF) (99.4%, 96.7%) and of the MTBDR
sl
test for resistance to fluoroquinolones (FQs) (100%, 100%) and second-line injectable drugs (SLIDs) (98.3%, 100%). The sensitivities of the array for detecting resistance to ethambutol and streptomycin were 79.3% and 64.9%, respectively. The array has potential as a powerful tool for clinical diagnosis and epidemiological investigations.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30872613</pmid><doi>10.1038/s41598-019-39339-3</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 45 45/23 45/61 45/77 631/61/32 692/699/255/1856 Antitubercular Agents - therapeutic use Bacterial Proteins - genetics Discordance DNA microarrays DNA, Bacterial - analysis DNA, Bacterial - genetics Drug resistance Drug Resistance, Multiple, Bacterial - genetics Epidemiology Ethambutol Extensively Drug-Resistant Tuberculosis - drug therapy Extensively Drug-Resistant Tuberculosis - microbiology Fluoroquinolones Genotype Humanities and Social Sciences Humans Isoniazid Microbial Sensitivity Tests multidisciplinary Multidrug resistance Mutation Mycobacterium tuberculosis - classification Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Oligonucleotide Array Sequence Analysis - methods Oligonucleotides Primers Rifampin RpoB protein Science Science (multidisciplinary) Sequence Analysis, DNA - methods Single-nucleotide polymorphism Streptomycin Tuberculosis |
| title | A new oligonucleotide array for the detection of multidrug and extensively drug-resistance tuberculosis |
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