Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia
Ethambutol (EMB) is an important anti-tuberculosis drug used in the management of multi-drug resistant tuberculosis (MDR-TB). Mutations in embB are the major mechanism of resistance. This study investigated embB mutations among MDR-TB isolates and analyzed their correlations with phenotypic drug sus...
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| Veröffentlicht in: | Tuberculosis (Edinburgh, Scotland) Scotland), 2022-03, Vol.133, p.102184-102184, Article 102184 |
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| container_title | Tuberculosis (Edinburgh, Scotland) |
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| creator | Bwalya, Precious Solo, Eddie S. Chizimu, Joseph Y. Shrestha, Dipti Mbulo, Grace Thapa, Jeewan Nakajima, Chie Suzuki, Yasuhiko |
| description | Ethambutol (EMB) is an important anti-tuberculosis drug used in the management of multi-drug resistant tuberculosis (MDR-TB). Mutations in embB are the major mechanism of resistance. This study investigated embB mutations among MDR-TB isolates and analyzed their correlations with phenotypic drug susceptibility testing (DST) in Zambia.
A total of 132 MDR-TB isolates were collected from January 2014 to April 2017 and characterized using MGIT 960 systems, embB sequencing, and spoligotyping.
Out of 61 phenotypically EMB resistant isolates, 53 had mutations in embB. Among the 71 EMB susceptible isolates, 47 had embB mutations. Sensitivity of embB mutations was 86.9% while specificity was 33.8%. CAS1_Kili (SIT21) had high odds of having embB mutations, particularly, G918A (Met306eIl) (Odds ratio 16.7, p |
| doi_str_mv | 10.1016/j.tube.2022.102184 |
| format | Article |
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A total of 132 MDR-TB isolates were collected from January 2014 to April 2017 and characterized using MGIT 960 systems, embB sequencing, and spoligotyping.
Out of 61 phenotypically EMB resistant isolates, 53 had mutations in embB. Among the 71 EMB susceptible isolates, 47 had embB mutations. Sensitivity of embB mutations was 86.9% while specificity was 33.8%. CAS1_Kili (SIT21) had high odds of having embB mutations, particularly, G918A (Met306eIl) (Odds ratio 16.7, p < 0.0001).
Molecular EMB resistance testing by DNA sequencing can improve detection of EMB resistance among MDR-TB patients in Zambia. Additionally, CAS1_Kili was associated with embB amino acid substitution Met306Ile suggesting transmission. A detailed investigation to track and determine transmission hotspot area for MDR-TB could help optimize control strategies.</description><identifier>ISSN: 1472-9792</identifier><identifier>EISSN: 1873-281X</identifier><identifier>DOI: 10.1016/j.tube.2022.102184</identifier><identifier>PMID: 35240539</identifier><language>eng</language><publisher>Scotland: Elsevier Ltd</publisher><subject>Amino acid substitution ; Amino acids ; Antitubercular Agents - metabolism ; Antitubercular Agents - pharmacology ; Antitubercular Agents - therapeutic use ; DNA sequencing ; Drug resistance ; embB mutations ; Ethambutol ; Ethambutol - pharmacology ; Ethambutol - therapeutic use ; Humans ; Microbial Sensitivity Tests ; Multi-drug resistance ; Multidrug resistance ; Mutation ; Mycobacterium tuberculosis ; Pentosyltransferases - genetics ; Spoligotyping ; Tuberculosis ; Tuberculosis, Multidrug-Resistant - diagnosis ; Tuberculosis, Multidrug-Resistant - drug therapy ; Tuberculosis, Multidrug-Resistant - genetics ; Zambia ; Zambia - epidemiology</subject><ispartof>Tuberculosis (Edinburgh, Scotland), 2022-03, Vol.133, p.102184-102184, Article 102184</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. Mar 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c538t-b2cfd62ac7b6d209accd2966e0a97b172b7576191b94ad0138577e901c63ab283</citedby><cites>FETCH-LOGICAL-c538t-b2cfd62ac7b6d209accd2966e0a97b172b7576191b94ad0138577e901c63ab283</cites><orcidid>0000-0002-1313-1494</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S147297922200021X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35240539$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bwalya, Precious</creatorcontrib><creatorcontrib>Solo, Eddie S.</creatorcontrib><creatorcontrib>Chizimu, Joseph Y.</creatorcontrib><creatorcontrib>Shrestha, Dipti</creatorcontrib><creatorcontrib>Mbulo, Grace</creatorcontrib><creatorcontrib>Thapa, Jeewan</creatorcontrib><creatorcontrib>Nakajima, Chie</creatorcontrib><creatorcontrib>Suzuki, Yasuhiko</creatorcontrib><title>Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia</title><title>Tuberculosis (Edinburgh, Scotland)</title><addtitle>Tuberculosis (Edinb)</addtitle><description>Ethambutol (EMB) is an important anti-tuberculosis drug used in the management of multi-drug resistant tuberculosis (MDR-TB). Mutations in embB are the major mechanism of resistance. This study investigated embB mutations among MDR-TB isolates and analyzed their correlations with phenotypic drug susceptibility testing (DST) in Zambia.
A total of 132 MDR-TB isolates were collected from January 2014 to April 2017 and characterized using MGIT 960 systems, embB sequencing, and spoligotyping.
Out of 61 phenotypically EMB resistant isolates, 53 had mutations in embB. Among the 71 EMB susceptible isolates, 47 had embB mutations. Sensitivity of embB mutations was 86.9% while specificity was 33.8%. CAS1_Kili (SIT21) had high odds of having embB mutations, particularly, G918A (Met306eIl) (Odds ratio 16.7, p < 0.0001).
Molecular EMB resistance testing by DNA sequencing can improve detection of EMB resistance among MDR-TB patients in Zambia. Additionally, CAS1_Kili was associated with embB amino acid substitution Met306Ile suggesting transmission. A detailed investigation to track and determine transmission hotspot area for MDR-TB could help optimize control strategies.</description><subject>Amino acid substitution</subject><subject>Amino acids</subject><subject>Antitubercular Agents - metabolism</subject><subject>Antitubercular Agents - pharmacology</subject><subject>Antitubercular Agents - therapeutic use</subject><subject>DNA sequencing</subject><subject>Drug resistance</subject><subject>embB mutations</subject><subject>Ethambutol</subject><subject>Ethambutol - pharmacology</subject><subject>Ethambutol - therapeutic use</subject><subject>Humans</subject><subject>Microbial Sensitivity Tests</subject><subject>Multi-drug resistance</subject><subject>Multidrug resistance</subject><subject>Mutation</subject><subject>Mycobacterium tuberculosis</subject><subject>Pentosyltransferases - genetics</subject><subject>Spoligotyping</subject><subject>Tuberculosis</subject><subject>Tuberculosis, Multidrug-Resistant - diagnosis</subject><subject>Tuberculosis, Multidrug-Resistant - drug therapy</subject><subject>Tuberculosis, Multidrug-Resistant - genetics</subject><subject>Zambia</subject><subject>Zambia - epidemiology</subject><issn>1472-9792</issn><issn>1873-281X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1TAQhiNURC_wAiyQpW7Y5OBLYscSm_YIClIRG5AQG8uXOdRHSVx8OVJ5BJ4ah5QuWHTl0fzf_BrP3zQvCd4QTPib_SYXAxuKKa0NSobuSXNCBsFaOpBvR7XuBG2lkPS4OU1pj-sQHvCz5pj1tMM9kyfN7-2NjtpmiP6Xzj7MKOwQTOYSTSX_bSTk50MYD-BqgSDf6MmUHEYUIfmU9WxhEaYyZt-6WH48CBl9urPBrO5lQsu20ZYxVBn5FEadYXFH36ul18-bpzs9Jnhx_541X9-_-7L90F5_vvq4vbhubc-G3Bpqd45TbYXhjmKprXVUcg5YS2GIoEb0ghNJjOy0w4QNvRAgMbGcaUMHdta8Xn1vY_hZIGU1-WRhHPUMoSRFOeOko7KXFT3_D92HEue6XaW6gXLCOasUXSkbQ0oRduo2-knHO0WwWpJSe7X8XS1JqTWpOvTq3rqYCdzDyL9oKvB2BaDe4uAhqmQ91Gs7H8Fm5YJ_zP8PuZ2nWw</recordid><startdate>202203</startdate><enddate>202203</enddate><creator>Bwalya, Precious</creator><creator>Solo, Eddie S.</creator><creator>Chizimu, Joseph Y.</creator><creator>Shrestha, Dipti</creator><creator>Mbulo, Grace</creator><creator>Thapa, Jeewan</creator><creator>Nakajima, Chie</creator><creator>Suzuki, Yasuhiko</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</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>7QL</scope><scope>C1K</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1313-1494</orcidid></search><sort><creationdate>202203</creationdate><title>Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia</title><author>Bwalya, Precious ; Solo, Eddie S. ; Chizimu, Joseph Y. ; Shrestha, Dipti ; Mbulo, Grace ; Thapa, Jeewan ; Nakajima, Chie ; Suzuki, Yasuhiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c538t-b2cfd62ac7b6d209accd2966e0a97b172b7576191b94ad0138577e901c63ab283</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Amino acid substitution</topic><topic>Amino acids</topic><topic>Antitubercular Agents - metabolism</topic><topic>Antitubercular Agents - pharmacology</topic><topic>Antitubercular Agents - therapeutic use</topic><topic>DNA sequencing</topic><topic>Drug resistance</topic><topic>embB mutations</topic><topic>Ethambutol</topic><topic>Ethambutol - pharmacology</topic><topic>Ethambutol - therapeutic use</topic><topic>Humans</topic><topic>Microbial Sensitivity Tests</topic><topic>Multi-drug resistance</topic><topic>Multidrug resistance</topic><topic>Mutation</topic><topic>Mycobacterium tuberculosis</topic><topic>Pentosyltransferases - genetics</topic><topic>Spoligotyping</topic><topic>Tuberculosis</topic><topic>Tuberculosis, Multidrug-Resistant - diagnosis</topic><topic>Tuberculosis, Multidrug-Resistant - drug therapy</topic><topic>Tuberculosis, Multidrug-Resistant - genetics</topic><topic>Zambia</topic><topic>Zambia - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bwalya, Precious</creatorcontrib><creatorcontrib>Solo, Eddie S.</creatorcontrib><creatorcontrib>Chizimu, Joseph Y.</creatorcontrib><creatorcontrib>Shrestha, Dipti</creatorcontrib><creatorcontrib>Mbulo, Grace</creatorcontrib><creatorcontrib>Thapa, Jeewan</creatorcontrib><creatorcontrib>Nakajima, Chie</creatorcontrib><creatorcontrib>Suzuki, Yasuhiko</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Tuberculosis (Edinburgh, Scotland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bwalya, Precious</au><au>Solo, Eddie S.</au><au>Chizimu, Joseph Y.</au><au>Shrestha, Dipti</au><au>Mbulo, Grace</au><au>Thapa, Jeewan</au><au>Nakajima, Chie</au><au>Suzuki, Yasuhiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia</atitle><jtitle>Tuberculosis (Edinburgh, Scotland)</jtitle><addtitle>Tuberculosis (Edinb)</addtitle><date>2022-03</date><risdate>2022</risdate><volume>133</volume><spage>102184</spage><epage>102184</epage><pages>102184-102184</pages><artnum>102184</artnum><issn>1472-9792</issn><eissn>1873-281X</eissn><abstract>Ethambutol (EMB) is an important anti-tuberculosis drug used in the management of multi-drug resistant tuberculosis (MDR-TB). Mutations in embB are the major mechanism of resistance. This study investigated embB mutations among MDR-TB isolates and analyzed their correlations with phenotypic drug susceptibility testing (DST) in Zambia.
A total of 132 MDR-TB isolates were collected from January 2014 to April 2017 and characterized using MGIT 960 systems, embB sequencing, and spoligotyping.
Out of 61 phenotypically EMB resistant isolates, 53 had mutations in embB. Among the 71 EMB susceptible isolates, 47 had embB mutations. Sensitivity of embB mutations was 86.9% while specificity was 33.8%. CAS1_Kili (SIT21) had high odds of having embB mutations, particularly, G918A (Met306eIl) (Odds ratio 16.7, p < 0.0001).
Molecular EMB resistance testing by DNA sequencing can improve detection of EMB resistance among MDR-TB patients in Zambia. Additionally, CAS1_Kili was associated with embB amino acid substitution Met306Ile suggesting transmission. A detailed investigation to track and determine transmission hotspot area for MDR-TB could help optimize control strategies.</abstract><cop>Scotland</cop><pub>Elsevier Ltd</pub><pmid>35240539</pmid><doi>10.1016/j.tube.2022.102184</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1313-1494</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Tuberculosis (Edinburgh, Scotland), 2022-03, Vol.133, p.102184-102184, Article 102184 |
| issn | 1472-9792 1873-281X |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Amino acid substitution Amino acids Antitubercular Agents - metabolism Antitubercular Agents - pharmacology Antitubercular Agents - therapeutic use DNA sequencing Drug resistance embB mutations Ethambutol Ethambutol - pharmacology Ethambutol - therapeutic use Humans Microbial Sensitivity Tests Multi-drug resistance Multidrug resistance Mutation Mycobacterium tuberculosis Pentosyltransferases - genetics Spoligotyping Tuberculosis Tuberculosis, Multidrug-Resistant - diagnosis Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - genetics Zambia Zambia - epidemiology |
| title | Characterization of embB mutations involved in ethambutol resistance in multi-drug resistant Mycobacterium tuberculosis isolates in Zambia |
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