Whole genome sequencing reveals novel resistance-conferring mutations and large genome deletions in drug-resistant Mycobacterium tuberculosis isolates from Indonesia

•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia.•Large genome deletions conferring isoniazid resistance were also identified.•Pre-existing mutations resistant to new and repurposed oral drugs were not detected. This study evaluated drug resistance profiles of...

Celý popis

Uložené v:

Podrobná bibliografia
Vydané v:	Journal of Global Antimicrobial Resistance Ročník 44; s. 314 - 318
Hlavní autori:	Aung, Htin Lin, Chaidir, Lidya, Pitaloka, Dian Ayu Eka, Miyahara, Yugen, Kumar, Narender, Soeroto, Arto Yuwono, Cook, Greg M, van Crevel, Reinout, Alisjahbana, Bachti, Peacock, Sharon J., Hill, Philip C
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier Ltd 01.09.2025 Elsevier
Predmet:	Antitubercular Agents - pharmacology Bacterial Proteins - genetics Catalase - genetics Drug Resistance, Multiple, Bacterial - genetics GeneXpert Genome, Bacterial Humans Indonesia Infectious Disease Isoniazid - pharmacology MDR-TB Microbial Sensitivity Tests Mutation Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Novel mutations Rifampin - pharmacology Sequence Deletion Tuberculosis Tuberculosis, Multidrug-Resistant - microbiology WGS Whole Genome Sequencing Indonesia WGS Tuberculosis Whole genome sequencing Novel mutations MDR-TB GeneXpert Indonesia
ISSN:	2213-7165, 2213-7173, 2213-7165, 2213-7173
On-line prístup:	Získať plný text
Tagy:	Pridať tag Žiadne tagy, Buďte prvý, kto otaguje tento záznam!

Abstract	•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia.•Large genome deletions conferring isoniazid resistance were also identified.•Pre-existing mutations resistant to new and repurposed oral drugs were not detected. This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches. We performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform. We found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD). Known drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand,the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance.
AbstractList	•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia.•Large genome deletions conferring isoniazid resistance were also identified.•Pre-existing mutations resistant to new and repurposed oral drugs were not detected. This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches. We performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform. We found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD). Known drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand,the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance. This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches.OBJECTIVEThis study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches.We performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform.METHODSWe performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform.We found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD).RESULTSWe found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD).Known drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand, the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance.CONCLUSIONSKnown drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand, the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance. Highlights•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia. •Large genome deletions conferring isoniazid resistance were also identified. •Pre-existing mutations resistant to new and repurposed oral drugs were not detected. Objective: This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches. Methods: We performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform. Results: We found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD). Conclusions: Known drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand,the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance. This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches. We performed phenotypic drug-susceptibility testing (DST), coupled with whole-genome sequencing (WGS) of 142 Mtb isolates identified as RIF-R (Rifampicin resistant) using the Xpert MTB/RIF platform. We found 107/142 (75%) isolates had high-level isoniazid resistance (INH-R) and rifampicin resistance (RIF-R). Of 107 isolates, we found two had novel katG mutations and three had large genome deletions encompassing the katG gene conferring INH-R. We also did not detect pre-existing mutations resistant to new and repurposed oral drugs bedaquiline (BDQ), pretomanid (Pa) and linezolid (LZD). Known drug-resistance conferring mutations reported in this study can be detected by the newly launched Xpert MTB/XDR together with Xpert MTB/RIF, providing clinicians with an expanded drug-susceptibility report without the need for culturing and WGS. On the other hand,the novel mutations and deletions found in this study are escaping routine diagnostics and could drive outbreaks of MDR-TB in Indonesia. The mass rollout of new and repurposed drugs for the treatment of drug-resistant TB in Indonesia is reassured by the absence of pre-existing mutations in this study. However, tools for rapid detection of resistance to these new drugs are urgently required to circumvent treatment-emergent resistance.
Author	Peacock, Sharon J. Soeroto, Arto Yuwono van Crevel, Reinout Miyahara, Yugen Chaidir, Lidya Cook, Greg M Hill, Philip C Kumar, Narender Aung, Htin Lin Pitaloka, Dian Ayu Eka Alisjahbana, Bachti
Author_xml	– sequence: 1 givenname: Htin Lin orcidid: 0000-0002-0465-6256 surname: Aung fullname: Aung, Htin Lin email: htin.aung@otago.ac.nz organization: Department of Microbiology and Immunology, Division of Health Sciences, University of Otago, Dunedin, New Zealand – sequence: 2 givenname: Lidya orcidid: 0000-0001-5661-4050 surname: Chaidir fullname: Chaidir, Lidya organization: Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia – sequence: 3 givenname: Dian Ayu Eka orcidid: 0000-0002-8187-8864 surname: Pitaloka fullname: Pitaloka, Dian Ayu Eka organization: Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia – sequence: 4 givenname: Yugen surname: Miyahara fullname: Miyahara, Yugen organization: Department of Microbiology and Immunology, Division of Health Sciences, University of Otago, Dunedin, New Zealand – sequence: 5 givenname: Narender surname: Kumar fullname: Kumar, Narender organization: Department of Medicine, University of Cambridge, Cambridge, United Kingdom – sequence: 6 givenname: Arto Yuwono surname: Soeroto fullname: Soeroto, Arto Yuwono organization: Department of Internal Medicine, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia – sequence: 7 givenname: Greg M orcidid: 0000-0001-8349-1500 surname: Cook fullname: Cook, Greg M organization: Department of Microbiology and Immunology, Division of Health Sciences, University of Otago, Dunedin, New Zealand – sequence: 8 givenname: Reinout orcidid: 0000-0002-6233-6410 surname: van Crevel fullname: van Crevel, Reinout organization: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, the Netherlands – sequence: 9 givenname: Bachti surname: Alisjahbana fullname: Alisjahbana, Bachti organization: Research Center for Care and Control of Infectious Disease, Universitas Padjadjaran, Bandung, Indonesia – sequence: 10 givenname: Sharon J. surname: Peacock fullname: Peacock, Sharon J. organization: Department of Medicine, University of Cambridge, Cambridge, United Kingdom – sequence: 11 givenname: Philip C surname: Hill fullname: Hill, Philip C organization: Centre for International Health, Division of Health Sciences, University of Otago, Dunedin, New Zealand
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/40706998$$D View this record in MEDLINE/PubMed
BookMark	eNqFUsuO1DAQjNAi9sH-AAfkI5cMjhM7CUJIaMXCSIs4AOJo-dEODo692MlI80H8Jw6zO0JIgC9221XV7u46L0588FAUTyq8qXDFno-bcRBxQzChG9xucNU-KM4IqeqyrRg9-e18WlymNOK8-qYirH1UnDa4xazvu7Pix5evwQEawIcJUILvC3hl_YAi7EC4hHzYgctRsmkWXkGpgjcQ44qZllnMNviEhNfIiTgclTQ4ODxZj3RchvJeYkbv9ypIoWaIdpnQvEiIanEhPyObghMzJGRimNDW61x0suJx8dDkz8Dl3X5RfL5-8-nqXXnz4e326vVNqSihcyk6iWWvpezblqi2M5gpI5qaKKEbKpkBDbiWlVTACOvaviYNpdAZiSHHfX1RbA-6OoiR30Y7ibjnQVj-6yLEgYs4W-WAC9nVgoLRtVZNJZgkzLAG14xSagzpstazg9ZtDLmraeaTTQqcEx7CknhN6prQDF_TPr2DLnICfUx8P6YMIAeAiiGlCOYIqTBf7cBHvtqBr3bguOXZDpn08kCC3LGdhciTsnm6oG0ENeeS7L_pr_6gK2e9VcJ9gz2kMSzR51nwiifCMf-4-m21G6E408la1Yu_C_wv-08s3eqy
Cites_doi	10.1016/j.gene.2016.02.003 10.1136/bmjgh-2021-007182 10.1016/S1473-3099(18)30496-1 10.3201/eid2711.210726 10.1038/s41579-019-0214-5 10.1038/s41588-018-0117-9 10.1038/s41579-024-01025-1 10.1183/13993003.00246-2018 10.1186/s13073-015-0164-0 10.1038/s41467-021-26248-1 10.1016/S1473-3099(18)30218-4 10.1056/NEJMoa1614915 10.1371/journal.pone.0296448 10.3201/eid2703.204364 10.1016/S1473-3099(23)00498-X 10.1016/j.tube.2022.102211 10.1016/S2666-5247(23)00172-6 10.1128/AAC.00974-18
ContentType	Journal Article
Copyright	2025 The Author(s) The Author(s) Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved. Copyright © 2025. Published by Elsevier Ltd.
Copyright_xml	– notice: 2025 The Author(s) – notice: The Author(s) – notice: Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved. – notice: Copyright © 2025. Published by Elsevier Ltd.
DBID	6I. AAFTH AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 DOA
DOI	10.1016/j.jgar.2025.07.017
DatabaseName	ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic DOAJ Directory of Open Access Journals
DatabaseTitle	CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic
DatabaseTitleList	MEDLINE - Academic MEDLINE
Database_xml	– sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website – sequence: 2 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 3 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database
DeliveryMethod	fulltext_linktorsrc
Discipline	Biology
EISSN	2213-7165 2213-7173
EndPage	318
ExternalDocumentID	oai_doaj_org_article_ab83a5efd3dc41a6b26f64036555ff28 40706998 10_1016_j_jgar_2025_07_017 S2213716525001729 1_s2_0_S2213716525001729
Genre	Journal Article
GeographicLocations	Indonesia
GeographicLocations_xml	– name: Indonesia
GroupedDBID	--M .1- .FO .~1 0R~ 1~. 4.4 457 4G. 53G 7-5 8P~ AAAJQ AABSN AAEDT AAEDW AAIKJ AAKOC AALRI AAOAW AAQFI AATTM AAXKI AAXUO AAYWO ABJNI ABMAC ABMZM ABXDB ACDAQ ACGFS ACIEU ACLOT ACRLP ACVFH ADBBV ADCNI ADEZE ADVLN AEBSH AEIPS AEKER AENEX AEUPX AFJKZ AFPUW AFRHN AFTJW AFXIZ AGEKW AGHFR AGLDT AGUBO AGYEJ AIEXJ AIGII AIIUN AIKHN AITUG AJRQY AJUYK AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ ANKPU ANZVX APXCP AXJTR BKOJK BLXMC BNPGV CJTIS COPKO EBS EFJIC EFKBS EFLBG EJD FDB FEDTE FIRID FNPLU FYGXN GBLVA GROUPED_DOAJ HVGLF HZ~ KOM LUGTX M41 MO0 O-L O9- OAUVE OK1 P-8 P-9 PC. Q38 ROL SDF SPCBC SSH SSI SSZ T5K Z5R ~G- ~HD 6I. AAFTH AAYXX CITATION M~E CGR CUY CVF ECM EIF NPM 7X8
ID	FETCH-LOGICAL-c525t-a8b0b9dbb9772c78f06cfa432cad45b6fede03b1bce62687932455e8fb0e26893
IEDL.DBID	DOA
ISICitedReferencesCount	0
ISICitedReferencesURI	http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=001559432000001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN	2213-7165 2213-7173
IngestDate	Fri Oct 03 12:51:07 EDT 2025 Thu Oct 02 22:20:24 EDT 2025 Mon Sep 22 02:44:33 EDT 2025 Sat Nov 29 06:53:15 EST 2025 Sun Oct 19 01:45:12 EDT 2025 Sun Oct 19 01:17:17 EDT 2025 Sun Oct 19 01:23:02 EDT 2025
IsDoiOpenAccess	true
IsOpenAccess	true
IsPeerReviewed	true
IsScholarly	true
Keywords	WGS Tuberculosis Whole genome sequencing Novel mutations MDR-TB GeneXpert Indonesia
Language	English
License	This is an open access article under the CC BY-NC-ND license. Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.
LinkModel	DirectLink
MergedId	FETCHMERGED-LOGICAL-c525t-a8b0b9dbb9772c78f06cfa432cad45b6fede03b1bce62687932455e8fb0e26893
Notes	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ORCID	0000-0002-8187-8864 0000-0001-8349-1500 0000-0001-5661-4050 0000-0002-0465-6256 0000-0002-6233-6410
OpenAccessLink	https://doaj.org/article/ab83a5efd3dc41a6b26f64036555ff28
PMID	40706998
PQID	3233256559
PQPubID	23479
PageCount	5
ParticipantIDs	doaj_primary_oai_doaj_org_article_ab83a5efd3dc41a6b26f64036555ff28 proquest_miscellaneous_3233256559 pubmed_primary_40706998 crossref_primary_10_1016_j_jgar_2025_07_017 elsevier_sciencedirect_doi_10_1016_j_jgar_2025_07_017 elsevier_clinicalkeyesjournals_1_s2_0_S2213716525001729 elsevier_clinicalkey_doi_10_1016_j_jgar_2025_07_017
PublicationCentury	2000
PublicationDate	2025-09-01
PublicationDateYYYYMMDD	2025-09-01
PublicationDate_xml	– month: 09 year: 2025 text: 2025-09-01 day: 01
PublicationDecade	2020
PublicationPlace	Netherlands
PublicationPlace_xml	– name: Netherlands
PublicationTitle	Journal of Global Antimicrobial Resistance
PublicationTitleAlternate	J Glob Antimicrob Resist
PublicationYear	2025
Publisher	Elsevier Ltd Elsevier
Publisher_xml	– name: Elsevier Ltd – name: Elsevier
References	Zhang, Wan, Zhou, Ni, Xu, Li (bib0008) 2016; 582 Rukmana, Gozali, Erlina (bib0017) 2024; 4 (bib0001) 2024 Farhat, Cox, Ghanem, Denkinger, Rodrigues, Abd El Aziz (bib0003) 2024; 22 Mulder, Rupert, Setiawan, Mambetova, Edo, Sugiharto (bib0018) 2022; 7 Derendinger, Dippenaar, de Vos, Huo, Alberts, Tadokera (bib0016) 2023; 4 Freschi, Vargas, Husain, Kamal, Skrahina, Tahseen (bib0024) 2021; 12 Xie, Chakravorty, Armstrong, Hall, Via, Song (bib0013) 2017; 377 Ashton, Cha, Anscombe, Thuong, Thwaites, Walker (bib0023) 2023; 9 Kandler, Mercante, Dalton, Ezewudo, Cowan, Burns (bib0009) 2018; 62 Yang, Lu, Warren, Wu, Jiang, Zuo (bib0021) 2018; 18 Wang, Lim, Phelan, Reyes, Palparan, Sanchez (bib0012) 2024; 14 Lestari, Nijman, Larasmanah, Soeroto, Santoso, Alisjahbana (bib0002) 2023; 22 (accessed 15 March 2025). Montoya, Malabad, Ang, Reyes, Basilio, Lim (bib0022) 2022; 135 complex. 2018. Gupta, Juneja, Babawale, Rustam Majidovich, Ndjeka, Thi Mai Nguyen (bib0019) 2024; 19 Auld, Shah, Mathema, Brown, Ismail, Omar (bib0025) 2018; 52 Aung, Nyunt, Fong, Biggs, Winkworth, Lockhart (bib0006) 2021; 27 Coll, McNerney, Preston, Guerra-Assunção, Warry, Hill-Cawthorne (bib0007) 2015; 7 WHO technical guide on the use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in Nonghanphithak, Chaiprasert, Smithtikarn, Kamolwat, Pungrassami, Chongsuvivatwong (bib0011) 2021; 27 Barilar, Fernando, Utpatel, Abujate, Madeira, José (bib0015) 2024; 24 Makhado, Matabane, Faccin, Pinçon, Jouet, Boutachkourt (bib0014) 2018; 18 WHO. Technical report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis. 2018. Holt, McAdam, Thai, Thuong, Ha, Lan (bib0020) 2018; 50 Meehan, Goig, Kohl, Verboven, Dippenaar, Ezewudo (bib0004) 2019 (accessed 25 June 2025). 10.1016/j.jgar.2025.07.017_bib0005 Derendinger (10.1016/j.jgar.2025.07.017_bib0016) 2023; 4 Lestari (10.1016/j.jgar.2025.07.017_bib0002) 2023; 22 (10.1016/j.jgar.2025.07.017_bib0001) 2024 Freschi (10.1016/j.jgar.2025.07.017_bib0024) 2021; 12 Farhat (10.1016/j.jgar.2025.07.017_bib0003) 2024; 22 Aung (10.1016/j.jgar.2025.07.017_bib0006) 2021; 27 Gupta (10.1016/j.jgar.2025.07.017_bib0019) 2024; 19 Makhado (10.1016/j.jgar.2025.07.017_bib0014) 2018; 18 Rukmana (10.1016/j.jgar.2025.07.017_bib0017) 2024; 4 Zhang (10.1016/j.jgar.2025.07.017_bib0008) 2016; 582 Meehan (10.1016/j.jgar.2025.07.017_bib0004) 2019 Coll (10.1016/j.jgar.2025.07.017_bib0007) 2015; 7 Holt (10.1016/j.jgar.2025.07.017_bib0020) 2018; 50 Montoya (10.1016/j.jgar.2025.07.017_bib0022) 2022; 135 Auld (10.1016/j.jgar.2025.07.017_bib0025) 2018; 52 Barilar (10.1016/j.jgar.2025.07.017_bib0015) 2024; 24 10.1016/j.jgar.2025.07.017_bib0010 Yang (10.1016/j.jgar.2025.07.017_bib0021) 2018; 18 Kandler (10.1016/j.jgar.2025.07.017_bib0009) 2018; 62 Nonghanphithak (10.1016/j.jgar.2025.07.017_bib0011) 2021; 27 Wang (10.1016/j.jgar.2025.07.017_bib0012) 2024; 14 Ashton (10.1016/j.jgar.2025.07.017_bib0023) 2023; 9 Xie (10.1016/j.jgar.2025.07.017_bib0013) 2017; 377 Mulder (10.1016/j.jgar.2025.07.017_bib0018) 2022; 7
References_xml	– volume: 52 year: 2018 ident: bib0025 article-title: Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities publication-title: Eur Respir J – volume: 50 start-page: 849 year: 2018 end-page: 856 ident: bib0020 article-title: Frequent transmission of the publication-title: Nat Genet – volume: 27 start-page: 2847 year: 2021 end-page: 2855 ident: bib0006 article-title: Genomic profiling of publication-title: Emerg Infect Dis – reference: WHO technical guide on the use of next-generation sequencing technologies for the detection of mutations associated with drug resistance in – volume: 14 year: 2024 ident: bib0012 article-title: Whole genome sequencing analysis of publication-title: Sci Rep – volume: 19 year: 2024 ident: bib0019 article-title: Global adoption of 6-month drug-resistant TB regimens: projected uptake by 2026 publication-title: PLoS One – reference: WHO. Technical report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis. 2018. – volume: 7 year: 2022 ident: bib0018 article-title: Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis publication-title: BMJ Glob Health – volume: 24 start-page: 297 year: 2024 end-page: 307 ident: bib0015 article-title: Emergence of bedaquiline-resistant tuberculosis and of multidrug-resistant and extensively drug-resistant publication-title: Lancet Infect Dis – reference: (accessed 25 June 2025). – volume: 4 year: 2024 ident: bib0017 article-title: Mycobacterium tuberculosis lineagedistributionusingwhole-genomesequencing and bedaquiline, clofazimine, and linezolidphenotypicprofiles among rifampicin-resistantisolates from West Java, Indonesia publication-title: Int J Microbiol – volume: 135 year: 2022 ident: bib0022 article-title: Molecular characterization of drug-resistant publication-title: Tuberculosis (Edinb) – volume: 377 start-page: 1043 year: 2017 end-page: 1054 ident: bib0013 article-title: Evaluation of a rapidmoleculardrug-susceptibilitytest for tuberculosis publication-title: N Engl J Med – volume: 18 start-page: 1350 year: 2018 end-page: 1359 ident: bib0014 article-title: Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study publication-title: Lancet Infect Dis – volume: 12 start-page: 6099 year: 2021 ident: bib0024 article-title: Population structure, biogeography and transmissibility of publication-title: Nat Commun – volume: 582 start-page: 128 year: 2016 end-page: 136 ident: bib0008 article-title: Whole genome analysis of an MDR Beijing/W strain of publication-title: Gene – volume: 7 start-page: 51 year: 2015 ident: bib0007 article-title: Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences publication-title: Genome Med – volume: 22 start-page: 617 year: 2024 end-page: 635 ident: bib0003 article-title: Drug-resistant tuberculosis: a persistent global health concern publication-title: Nat Rev Microbiol – volume: 9 year: 2023 ident: bib0023 article-title: Distribution and origins of publication-title: Microb Genom – volume: 62 year: 2018 ident: bib0009 article-title: Validation of novel publication-title: Antimicrob Agents Chemother – year: 2024 ident: bib0001 article-title: Global tuberculosis report – volume: 22 year: 2023 ident: bib0002 article-title: Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis publication-title: Lancet Reg Health Southeast Asia – reference: (accessed 15 March 2025). – volume: 4 start-page: e972 year: 2023 end-page: e982 ident: bib0016 article-title: Bedaquiline resistance in patients with drug-resistant tuberculosis in Cape Town, South Africa: a retrospective longitudinal cohort study publication-title: Lancet Microbe – reference: complex. 2018. – volume: 18 start-page: 788 year: 2018 end-page: 795 ident: bib0021 article-title: Internal migration and transmission dynamics of tuberculosis in Shanghai, China: an epidemiological, spatial, genomic analysis publication-title: Lancet Infect Dis – start-page: 533 year: 2019 end-page: 545 ident: bib0004 article-title: Whole genome sequencing of publication-title: Nat Rev Microbiol – volume: 27 start-page: 813 year: 2021 end-page: 822 ident: bib0011 article-title: Clusters of drug-resistant publication-title: Emerg Infect Dis – volume: 582 start-page: 128 issue: 2 year: 2016 ident: 10.1016/j.jgar.2025.07.017_bib0008 article-title: Whole genome analysis of an MDR Beijing/W strain of mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid publication-title: Gene doi: 10.1016/j.gene.2016.02.003 – volume: 7 issue: 1 year: 2022 ident: 10.1016/j.jgar.2025.07.017_bib0018 article-title: Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis publication-title: BMJ Glob Health doi: 10.1136/bmjgh-2021-007182 – volume: 18 start-page: 1350 issue: 12 year: 2018 ident: 10.1016/j.jgar.2025.07.017_bib0014 article-title: Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study publication-title: Lancet Infect Dis doi: 10.1016/S1473-3099(18)30496-1 – year: 2024 ident: 10.1016/j.jgar.2025.07.017_bib0001 – volume: 27 start-page: 2847 issue: 11 year: 2021 ident: 10.1016/j.jgar.2025.07.017_bib0006 article-title: Genomic profiling of mycobacterium tuberculosisstrains, Myanmar publication-title: Emerg Infect Dis doi: 10.3201/eid2711.210726 – start-page: 533 issue: 9 year: 2019 ident: 10.1016/j.jgar.2025.07.017_bib0004 article-title: Whole genome sequencing of mycobacterium tuberculosis: current standards and open issues publication-title: Nat Rev Microbiol doi: 10.1038/s41579-019-0214-5 – volume: 14 issue: 1 year: 2024 ident: 10.1016/j.jgar.2025.07.017_bib0012 article-title: Whole genome sequencing analysis of mycobacterium tuberculosis reveals circulating strain types and drug-resistance mutations in the Philippines publication-title: Sci Rep – volume: 50 start-page: 849 issue: 6 year: 2018 ident: 10.1016/j.jgar.2025.07.017_bib0020 article-title: Frequent transmission of the mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam publication-title: Nat Genet doi: 10.1038/s41588-018-0117-9 – volume: 22 start-page: 617 issue: 10 year: 2024 ident: 10.1016/j.jgar.2025.07.017_bib0003 article-title: Drug-resistant tuberculosis: a persistent global health concern publication-title: Nat Rev Microbiol doi: 10.1038/s41579-024-01025-1 – volume: 52 issue: 4 year: 2018 ident: 10.1016/j.jgar.2025.07.017_bib0025 article-title: Extensively drug-resistant tuberculosis in South Africa: genomic evidence supporting transmission in communities publication-title: Eur Respir J doi: 10.1183/13993003.00246-2018 – volume: 7 start-page: 51 issue: 1 year: 2015 ident: 10.1016/j.jgar.2025.07.017_bib0007 article-title: Rapid determination of anti-tuberculosis drug resistance from whole-genome sequences publication-title: Genome Med doi: 10.1186/s13073-015-0164-0 – ident: 10.1016/j.jgar.2025.07.017_bib0010 – volume: 12 start-page: 6099 issue: 1 year: 2021 ident: 10.1016/j.jgar.2025.07.017_bib0024 article-title: Population structure, biogeography and transmissibility of mycobacterium tuberculosis publication-title: Nat Commun doi: 10.1038/s41467-021-26248-1 – volume: 22 year: 2023 ident: 10.1016/j.jgar.2025.07.017_bib0002 article-title: Management of drug-resistant tuberculosis in Indonesia: a four-year cascade of care analysis publication-title: Lancet Reg Health Southeast Asia – volume: 18 start-page: 788 issue: 7 year: 2018 ident: 10.1016/j.jgar.2025.07.017_bib0021 article-title: Internal migration and transmission dynamics of tuberculosis in Shanghai, China: an epidemiological, spatial, genomic analysis publication-title: Lancet Infect Dis doi: 10.1016/S1473-3099(18)30218-4 – volume: 377 start-page: 1043 year: 2017 ident: 10.1016/j.jgar.2025.07.017_bib0013 article-title: Evaluation of a rapidmoleculardrug-susceptibilitytest for tuberculosis publication-title: N Engl J Med doi: 10.1056/NEJMoa1614915 – volume: 19 issue: 1 year: 2024 ident: 10.1016/j.jgar.2025.07.017_bib0019 article-title: Global adoption of 6-month drug-resistant TB regimens: projected uptake by 2026 publication-title: PLoS One doi: 10.1371/journal.pone.0296448 – volume: 27 start-page: 813 issue: 3 year: 2021 ident: 10.1016/j.jgar.2025.07.017_bib0011 article-title: Clusters of drug-resistantmycobacterium tuberculosisdetected by whole-genomesequenceanalysis of nationwidesample, Thailand, 2014-2017 publication-title: Emerg Infect Dis doi: 10.3201/eid2703.204364 – volume: 24 start-page: 297 issue: 3 year: 2024 ident: 10.1016/j.jgar.2025.07.017_bib0015 article-title: Emergence of bedaquiline-resistant tuberculosis and of multidrug-resistant and extensively drug-resistant mycobacterium tuberculosis strains with rpoB Ile491Phe mutation not detected by Xpert MTB/RIF in Mozambique: a retrospective observational study publication-title: Lancet Infect Dis doi: 10.1016/S1473-3099(23)00498-X – volume: 135 year: 2022 ident: 10.1016/j.jgar.2025.07.017_bib0022 article-title: Molecular characterization of drug-resistant mycobacterium tuberculosis among Filipino patients derived from the national tuberculosis prevalence survey Philippines 2016 publication-title: Tuberculosis (Edinb) doi: 10.1016/j.tube.2022.102211 – volume: 4 year: 2024 ident: 10.1016/j.jgar.2025.07.017_bib0017 article-title: Mycobacterium tuberculosis lineagedistributionusingwhole-genomesequencing and bedaquiline, clofazimine, and linezolidphenotypicprofiles among rifampicin-resistantisolates from West Java, Indonesia publication-title: Int J Microbiol – ident: 10.1016/j.jgar.2025.07.017_bib0005 – volume: 4 start-page: e972 issue: 12 year: 2023 ident: 10.1016/j.jgar.2025.07.017_bib0016 article-title: Bedaquiline resistance in patients with drug-resistant tuberculosis in Cape Town, South Africa: a retrospective longitudinal cohort study publication-title: Lancet Microbe doi: 10.1016/S2666-5247(23)00172-6 – volume: 9 issue: 2 year: 2023 ident: 10.1016/j.jgar.2025.07.017_bib0023 article-title: Distribution and origins of mycobacterium tuberculosis L4 in Southeast Asia publication-title: Microb Genom – volume: 62 issue: 10 year: 2018 ident: 10.1016/j.jgar.2025.07.017_bib0009 article-title: Validation of novel mycobacterium tuberculosis isoniazid resistance mutations not detectable by common molecular tests publication-title: Antimicrob Agents Chemother doi: 10.1128/AAC.00974-18
SSID	ssj0000941267 ssib050733640
Score	2.320035
Snippet	•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia.•Large genome deletions conferring isoniazid resistance were also... Highlights•Novel mutations were identified in drug-resistant M. tuberculosis isolates in Indonesia. •Large genome deletions conferring isoniazid resistance... This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic approaches.... This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic... Objective: This study evaluated drug resistance profiles of Mycobacterium tuberculosis (Mtb) isolates in West Java, Indonesia through phenotypic and genomic...
SourceID	doaj proquest pubmed crossref elsevier
SourceType	Open Website Aggregation Database Index Database Publisher
StartPage	314
SubjectTerms	Antitubercular Agents - pharmacology Bacterial Proteins - genetics Catalase - genetics Drug Resistance, Multiple, Bacterial - genetics GeneXpert Genome, Bacterial Humans Indonesia Infectious Disease Isoniazid - pharmacology MDR-TB Microbial Sensitivity Tests Mutation Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Novel mutations Rifampin - pharmacology Sequence Deletion Tuberculosis Tuberculosis, Multidrug-Resistant - microbiology WGS Whole Genome Sequencing
Title	Whole genome sequencing reveals novel resistance-conferring mutations and large genome deletions in drug-resistant Mycobacterium tuberculosis isolates from Indonesia
URI	https://www.clinicalkey.com/#!/content/1-s2.0-S2213716525001729 https://www.clinicalkey.es/playcontent/1-s2.0-S2213716525001729 https://dx.doi.org/10.1016/j.jgar.2025.07.017 https://www.ncbi.nlm.nih.gov/pubmed/40706998 https://www.proquest.com/docview/3233256559 https://doaj.org/article/ab83a5efd3dc41a6b26f64036555ff28
Volume	44
WOSCitedRecordID	wos001559432000001&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
hasFullText	1
inHoldings	1
isFullTextHit
isPrint
journalDatabaseRights	– providerCode: PRVAON databaseName: DOAJ Directory of Open Access Journals customDbUrl: eissn: 2213-7165 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000941267 issn: 2213-7165 databaseCode: DOA dateStart: 20200101 isFulltext: true titleUrlDefault: https://www.doaj.org/ providerName: Directory of Open Access Journals – providerCode: PRVESC databaseName: Elsevier SD Freedom Collection Journals 2021 customDbUrl: eissn: 2213-7165 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0000941267 issn: 2213-7165 databaseCode: AIEXJ dateStart: 20200301 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier – providerCode: PRVHPJ databaseName: ROAD: Directory of Open Access Scholarly Resources customDbUrl: eissn: 2213-7165 dateEnd: 99991231 omitProxy: false ssIdentifier: ssib050733640 issn: 2213-7165 databaseCode: M~E dateStart: 20130101 isFulltext: true titleUrlDefault: https://road.issn.org providerName: ISSN International Centre
link	http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV3di9QwEA96Kvgifp71Y4ngmxTTpGnTx1P28IQ7BBX3LSRpKrvsdmXbHtyL_43_pzNJu56g3osvhX4kKZnJ5DftzG8IeQkogRVGlKnPfJnmnNWpMbCuRCOl464uM8NCsYny7EwtFtWHS6W-MCYs0gPHiXttrBJG-qYWtcszU1heNEUOdldK2TQ8pPmysrrkTK1ivFzGQ_lYzjORglMgx4yZGNy1QopX8PtlYO4M1cp-7UqBvP-3zelv4DNsQsd3yZ0RPdKj-Nb3yDXf3ie3Yj3JiwfkxxesdkuRd3Xj6RglDXsTRZ4m0DPabs_9Gs46RI0g7tSFhD_8tkc3Q_wr31HT1nSNEeJTT1gsJ95atrTeDV_TqYuenl44MAmB8nnY0H6wfueG9RZu0yXoNUJZijks9ATrhkAz85B8Pp5_evsuHeswpE5y2adGWWar2lrAityVqmGFa0wuuDN1Lm3R-NozYTPrPLhHClY8z6X0qrHMw3klHpGDFkZ4TKhpkJ8MjApTPjcA7JVXhheilF4CNlIJeTXJQX-LdBt6ikNbaZSaRqlpVmqQWkLeoKj2TyJVdrgACqRHBdJXKVBCxCRoPWWjgv2Ejpb_HLr8UyvfjSag05nuuGb6Iyog6h9gTfS3q4TIfcsR5UT0cuWILyYt1GAC8L-Oaf126LTgQgByBd8wIYdRPfdTAv46K8ClfvI_puopuY0vFEPsnpGDfjf45-SmO--X3W5GrpcLNSM3jk7mi_ezsB7hePp9_hMcQTro
linkProvider	Directory of Open Access Journals
openUrl	ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Whole+genome+sequencing+reveals+novel+resistance-conferring+mutations+and+large+genome+deletions+in+drug-resistant+Mycobacterium+tuberculosis+isolates+from+Indonesia&rft.jtitle=Journal+of+global+antimicrobial+resistance.&rft.au=Aung%2C+Htin+Lin&rft.au=Chaidir%2C+Lidya&rft.au=Pitaloka%2C+Dian+Ayu+Eka&rft.au=Miyahara%2C+Yugen&rft.date=2025-09-01&rft.issn=2213-7173&rft.eissn=2213-7165&rft_id=info:doi/10.1016%2Fj.jgar.2025.07.017&rft.externalDBID=NO_FULL_TEXT
thumbnail_l	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2213-7165&client=summon
thumbnail_m	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2213-7165&client=summon
thumbnail_s	http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2213-7165&client=summon