Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations
Nepal exhibits a tuberculosis (TB) incidence rate that is comparable to neighbouring high TB incidence countries. In addition, it records >500 cases of multi-drug resistant (MDR) TB each year. The objective of this study was to perform whole-genome bioinformatic analysis on MDR-TB isolates from N...
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| Veröffentlicht in: | Genomics (San Diego, Calif.) Calif.), 2022-03, Vol.114 (2), p.110278-110278, Article 110278 |
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| creator | Leong, Kelvin W.C. Gautam, Sanjay S. Pradhan, Manoj Singh, Y. Ibotomba KC, Rajendra Rajbhandari, Sagar K. Ghimire, Gokarna R. Adhikari, Krishna Shrestha, Uma Chaudhary, Raina Ghimire, Gyanendra Khadka, Sundar O'Toole, Ronan F. |
| description | Nepal exhibits a tuberculosis (TB) incidence rate that is comparable to neighbouring high TB incidence countries. In addition, it records >500 cases of multi-drug resistant (MDR) TB each year. The objective of this study was to perform whole-genome bioinformatic analysis on MDR-TB isolates from Nepal (n = 19) to identify the specific mutations underlying their phenotypic resistance. In addition, we examined the dominant genotype among the Nepal MDR-TB isolates, the East-Asian Beijing sub-lineage, to determine its relatedness to a panel of 1274 genomes of international strains available from public databases. These analyses provided evidence that the XDR-TB isolates in our collection were not derived from importation of primary XDR-TB to Nepal but were more likely the result of acquisition of second-line drug resistance in Nepal. Resistance to fluoroquinolones was detected among a high proportion of the Nepal isolates. This has implications for the management of TB, including appropriate antimicrobial stewardship and susceptibility testing for fluoroquinolones and other second-line TB drugs, to minimise the development of XDR-TB among Nepal TB cases.
•Genetic mutations for resistance to first- and second-line TB drugs were determined in MDR/XDR M. tuberculosis from Nepal.•SNP and cgMLST analyses indicate that the XDR-TB isolates examined here emerged from local MDR-TB isolates in Nepal. |
| doi_str_mv | 10.1016/j.ygeno.2022.110278 |
| format | Article |
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•Genetic mutations for resistance to first- and second-line TB drugs were determined in MDR/XDR M. tuberculosis from Nepal.•SNP and cgMLST analyses indicate that the XDR-TB isolates examined here emerged from local MDR-TB isolates in Nepal.</description><identifier>ISSN: 0888-7543</identifier><identifier>EISSN: 1089-8646</identifier><identifier>DOI: 10.1016/j.ygeno.2022.110278</identifier><identifier>PMID: 35143885</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Antitubercular Agents - pharmacology ; Antitubercular Agents - therapeutic use ; bioinformatics ; China ; Drug Resistance, Multiple, Bacterial - genetics ; Extensively Drug-Resistant Tuberculosis - drug therapy ; Extensively Drug-Resistant Tuberculosis - epidemiology ; Extensively Drug-Resistant Tuberculosis - microbiology ; Extensively-drug resistant tuberculosis (XDR-TB) ; Fluoroquinolones ; genome ; Genomics ; genotype ; Humans ; Multi-drug resistant tuberculosis (MDR-TB) ; multiple drug resistance ; Mycobacterium tuberculosis ; Mycobacterium tuberculosis - genetics ; Nepal ; Nepal - epidemiology ; phenotype ; tuberculosis ; Tuberculosis, Multidrug-Resistant - drug therapy ; Tuberculosis, Multidrug-Resistant - epidemiology ; Tuberculosis, Multidrug-Resistant - microbiology ; Whole genome analysis</subject><ispartof>Genomics (San Diego, Calif.), 2022-03, Vol.114 (2), p.110278-110278, Article 110278</ispartof><rights>2022 The Authors</rights><rights>Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-88acdda36d568ec2bbf7415b61b559dcc60a7cc09581a468793db4c8313aa293</citedby><cites>FETCH-LOGICAL-c437t-88acdda36d568ec2bbf7415b61b559dcc60a7cc09581a468793db4c8313aa293</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0888754322000234$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,860,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35143885$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Leong, Kelvin W.C.</creatorcontrib><creatorcontrib>Gautam, Sanjay S.</creatorcontrib><creatorcontrib>Pradhan, Manoj</creatorcontrib><creatorcontrib>Singh, Y. Ibotomba</creatorcontrib><creatorcontrib>KC, Rajendra</creatorcontrib><creatorcontrib>Rajbhandari, Sagar K.</creatorcontrib><creatorcontrib>Ghimire, Gokarna R.</creatorcontrib><creatorcontrib>Adhikari, Krishna</creatorcontrib><creatorcontrib>Shrestha, Uma</creatorcontrib><creatorcontrib>Chaudhary, Raina</creatorcontrib><creatorcontrib>Ghimire, Gyanendra</creatorcontrib><creatorcontrib>Khadka, Sundar</creatorcontrib><creatorcontrib>O'Toole, Ronan F.</creatorcontrib><title>Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations</title><title>Genomics (San Diego, Calif.)</title><addtitle>Genomics</addtitle><description>Nepal exhibits a tuberculosis (TB) incidence rate that is comparable to neighbouring high TB incidence countries. In addition, it records >500 cases of multi-drug resistant (MDR) TB each year. The objective of this study was to perform whole-genome bioinformatic analysis on MDR-TB isolates from Nepal (n = 19) to identify the specific mutations underlying their phenotypic resistance. In addition, we examined the dominant genotype among the Nepal MDR-TB isolates, the East-Asian Beijing sub-lineage, to determine its relatedness to a panel of 1274 genomes of international strains available from public databases. These analyses provided evidence that the XDR-TB isolates in our collection were not derived from importation of primary XDR-TB to Nepal but were more likely the result of acquisition of second-line drug resistance in Nepal. Resistance to fluoroquinolones was detected among a high proportion of the Nepal isolates. This has implications for the management of TB, including appropriate antimicrobial stewardship and susceptibility testing for fluoroquinolones and other second-line TB drugs, to minimise the development of XDR-TB among Nepal TB cases.
•Genetic mutations for resistance to first- and second-line TB drugs were determined in MDR/XDR M. tuberculosis from Nepal.•SNP and cgMLST analyses indicate that the XDR-TB isolates examined here emerged from local MDR-TB isolates in Nepal.</description><subject>Antitubercular Agents - pharmacology</subject><subject>Antitubercular Agents - therapeutic use</subject><subject>bioinformatics</subject><subject>China</subject><subject>Drug Resistance, Multiple, Bacterial - genetics</subject><subject>Extensively Drug-Resistant Tuberculosis - drug therapy</subject><subject>Extensively Drug-Resistant Tuberculosis - epidemiology</subject><subject>Extensively Drug-Resistant Tuberculosis - microbiology</subject><subject>Extensively-drug resistant tuberculosis (XDR-TB)</subject><subject>Fluoroquinolones</subject><subject>genome</subject><subject>Genomics</subject><subject>genotype</subject><subject>Humans</subject><subject>Multi-drug resistant tuberculosis (MDR-TB)</subject><subject>multiple drug resistance</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Nepal</subject><subject>Nepal - epidemiology</subject><subject>phenotype</subject><subject>tuberculosis</subject><subject>Tuberculosis, Multidrug-Resistant - drug therapy</subject><subject>Tuberculosis, Multidrug-Resistant - epidemiology</subject><subject>Tuberculosis, Multidrug-Resistant - microbiology</subject><subject>Whole genome analysis</subject><issn>0888-7543</issn><issn>1089-8646</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi1ERZeWX4CEfOSSxY6dZHLggFblQyrtpXfLGU-2XiVxsJ1KK_48WbZwRJxG8jzzvpIfxt5KsZVC1h8O2-OeprAtRVlupRRlAy_YRgpoC6h1_ZJtBAAUTaXVJXud0kEI0SooX7FLVUmtAKoN-7kL42yjzf6J-Clu9MjtZIdjosRDz8dlyL5wcdnzSMmnbKfMvx8xdBYzRb-MPC8dRVyGsK55H8PI72i2wxrjeMiPFNfgsI92fvS4Pg8B17owpWt20dsh0ZvnecUePt887L4Wt_dfvu0-3RaoVZMLAIvOWVW7qgbCsuv6Rsuqq2VXVa1DrIVtEEVbgbS6hqZVrtMISipry1Zdsffn2DmGHwulbEafkIbBThSWZMpaA-gWGvEfaAlKSC30iqozijGkFKk3c_SjjUcjhTn5MQfz2485-TFnP-vVu-eCpRvJ_b35I2QFPp4BWj_kyVM0CT1NSM5Hwmxc8P8s-AXYgKUX</recordid><startdate>202203</startdate><enddate>202203</enddate><creator>Leong, Kelvin W.C.</creator><creator>Gautam, Sanjay S.</creator><creator>Pradhan, Manoj</creator><creator>Singh, Y. Ibotomba</creator><creator>KC, Rajendra</creator><creator>Rajbhandari, Sagar K.</creator><creator>Ghimire, Gokarna R.</creator><creator>Adhikari, Krishna</creator><creator>Shrestha, Uma</creator><creator>Chaudhary, Raina</creator><creator>Ghimire, Gyanendra</creator><creator>Khadka, Sundar</creator><creator>O'Toole, Ronan F.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>202203</creationdate><title>Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations</title><author>Leong, Kelvin W.C. ; Gautam, Sanjay S. ; Pradhan, Manoj ; Singh, Y. Ibotomba ; KC, Rajendra ; Rajbhandari, Sagar K. ; Ghimire, Gokarna R. ; Adhikari, Krishna ; Shrestha, Uma ; Chaudhary, Raina ; Ghimire, Gyanendra ; Khadka, Sundar ; O'Toole, Ronan F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-88acdda36d568ec2bbf7415b61b559dcc60a7cc09581a468793db4c8313aa293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antitubercular Agents - pharmacology</topic><topic>Antitubercular Agents - therapeutic use</topic><topic>bioinformatics</topic><topic>China</topic><topic>Drug Resistance, Multiple, Bacterial - genetics</topic><topic>Extensively Drug-Resistant Tuberculosis - drug therapy</topic><topic>Extensively Drug-Resistant Tuberculosis - epidemiology</topic><topic>Extensively Drug-Resistant Tuberculosis - microbiology</topic><topic>Extensively-drug resistant tuberculosis (XDR-TB)</topic><topic>Fluoroquinolones</topic><topic>genome</topic><topic>Genomics</topic><topic>genotype</topic><topic>Humans</topic><topic>Multi-drug resistant tuberculosis (MDR-TB)</topic><topic>multiple drug resistance</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Nepal</topic><topic>Nepal - epidemiology</topic><topic>phenotype</topic><topic>tuberculosis</topic><topic>Tuberculosis, Multidrug-Resistant - drug therapy</topic><topic>Tuberculosis, Multidrug-Resistant - epidemiology</topic><topic>Tuberculosis, Multidrug-Resistant - microbiology</topic><topic>Whole genome analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Leong, Kelvin W.C.</creatorcontrib><creatorcontrib>Gautam, Sanjay S.</creatorcontrib><creatorcontrib>Pradhan, Manoj</creatorcontrib><creatorcontrib>Singh, Y. Ibotomba</creatorcontrib><creatorcontrib>KC, Rajendra</creatorcontrib><creatorcontrib>Rajbhandari, Sagar K.</creatorcontrib><creatorcontrib>Ghimire, Gokarna R.</creatorcontrib><creatorcontrib>Adhikari, Krishna</creatorcontrib><creatorcontrib>Shrestha, Uma</creatorcontrib><creatorcontrib>Chaudhary, Raina</creatorcontrib><creatorcontrib>Ghimire, Gyanendra</creatorcontrib><creatorcontrib>Khadka, Sundar</creatorcontrib><creatorcontrib>O'Toole, Ronan F.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Genomics (San Diego, Calif.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Leong, Kelvin W.C.</au><au>Gautam, Sanjay S.</au><au>Pradhan, Manoj</au><au>Singh, Y. Ibotomba</au><au>KC, Rajendra</au><au>Rajbhandari, Sagar K.</au><au>Ghimire, Gokarna R.</au><au>Adhikari, Krishna</au><au>Shrestha, Uma</au><au>Chaudhary, Raina</au><au>Ghimire, Gyanendra</au><au>Khadka, Sundar</au><au>O'Toole, Ronan F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations</atitle><jtitle>Genomics (San Diego, Calif.)</jtitle><addtitle>Genomics</addtitle><date>2022-03</date><risdate>2022</risdate><volume>114</volume><issue>2</issue><spage>110278</spage><epage>110278</epage><pages>110278-110278</pages><artnum>110278</artnum><issn>0888-7543</issn><eissn>1089-8646</eissn><abstract>Nepal exhibits a tuberculosis (TB) incidence rate that is comparable to neighbouring high TB incidence countries. In addition, it records >500 cases of multi-drug resistant (MDR) TB each year. The objective of this study was to perform whole-genome bioinformatic analysis on MDR-TB isolates from Nepal (n = 19) to identify the specific mutations underlying their phenotypic resistance. In addition, we examined the dominant genotype among the Nepal MDR-TB isolates, the East-Asian Beijing sub-lineage, to determine its relatedness to a panel of 1274 genomes of international strains available from public databases. These analyses provided evidence that the XDR-TB isolates in our collection were not derived from importation of primary XDR-TB to Nepal but were more likely the result of acquisition of second-line drug resistance in Nepal. Resistance to fluoroquinolones was detected among a high proportion of the Nepal isolates. This has implications for the management of TB, including appropriate antimicrobial stewardship and susceptibility testing for fluoroquinolones and other second-line TB drugs, to minimise the development of XDR-TB among Nepal TB cases.
•Genetic mutations for resistance to first- and second-line TB drugs were determined in MDR/XDR M. tuberculosis from Nepal.•SNP and cgMLST analyses indicate that the XDR-TB isolates examined here emerged from local MDR-TB isolates in Nepal.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>35143885</pmid><doi>10.1016/j.ygeno.2022.110278</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antitubercular Agents - pharmacology Antitubercular Agents - therapeutic use bioinformatics China Drug Resistance, Multiple, Bacterial - genetics Extensively Drug-Resistant Tuberculosis - drug therapy Extensively Drug-Resistant Tuberculosis - epidemiology Extensively Drug-Resistant Tuberculosis - microbiology Extensively-drug resistant tuberculosis (XDR-TB) Fluoroquinolones genome Genomics genotype Humans Multi-drug resistant tuberculosis (MDR-TB) multiple drug resistance Mycobacterium tuberculosis Mycobacterium tuberculosis - genetics Nepal Nepal - epidemiology phenotype tuberculosis Tuberculosis, Multidrug-Resistant - drug therapy Tuberculosis, Multidrug-Resistant - epidemiology Tuberculosis, Multidrug-Resistant - microbiology Whole genome analysis |
| title | Comparative genomic analyses of multi-drug resistant Mycobacterium tuberculosis from Nepal and other geographical locations |
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