{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:47:46Z","timestamp":1793382466640,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Tropical Med Int Health"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vietnam is a hotspot for the emergence and spread of multidrug\u2010resistant <jats:italic>Mycobacterium tuberculosis<\/jats:italic>. This study aimed to perform a retrospective study on the compensatory evolution in multidrug\u2010resistant <jats:italic>M. tuberculosis<\/jats:italic> strains and the association with drug\u2010resistant mutations and <jats:italic>M. tuberculosis<\/jats:italic> genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Hundred and seventy\u2010three strains resistant to rifampicin (<jats:italic>n<\/jats:italic>\u2009=\u2009126) and\/or isoniazid (<jats:italic>n<\/jats:italic>\u2009=\u2009170) (multidrug\u2010resistant\u2009=\u2009123) were selected according to different drug\u2010resistant patterns and genotypes. The genes\/promoter regions including <jats:italic>rpo<\/jats:italic>A, <jats:italic>rpo<\/jats:italic>B, <jats:italic>rpo<\/jats:italic>C, <jats:italic>kat<\/jats:italic>G, <jats:italic>inh<\/jats:italic>A, <jats:italic>inh<\/jats:italic>A promoter, <jats:italic>ahp<\/jats:italic>C, <jats:italic>ahp<\/jats:italic>C promoter, <jats:italic>gyr<\/jats:italic>A, <jats:italic>gyr<\/jats:italic>B, and <jats:italic>rrs<\/jats:italic> were sequenced for each strain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Frequency of rifampicin\u2010 and isoniazid\u2010resistant mutations in multidrug\u2010resistant strains was 99.2% and 97.0%, respectively. Mutations associated with low \u2013high levels of drug resistance with low\u2010 or no\u2010fitness costs compared to the wild type, including <jats:italic>rpo<\/jats:italic>B_Ser450Leu, <jats:italic>kat<\/jats:italic>G_Ser315Thr, <jats:italic>inh<\/jats:italic>A\u201015(A\u2010T), <jats:italic>gyr<\/jats:italic>A_Asp94Gly, and <jats:italic>rrs<\/jats:italic>_A1401GA, accounted for 46.3%, 76.4%, 16.2%, 8.9%, and 11.4%, respectively, in the multidrug\u2010resistant strains. Beijing and Euro\u2010American genotype strains were associated with high\u2010level drug\u2010resistant mutations, <jats:italic>rpo<\/jats:italic>B_Ser450Leu, <jats:italic>kat<\/jats:italic>G_Ser315Thr, and <jats:italic>gyr<\/jats:italic>A_Asp94Gly, while East African\u2013Indian genotype strains were associated with low to high\u2010level drug\u2010resistant mutations, <jats:italic>rpo<\/jats:italic>B_His445Asp, <jats:italic>rpo<\/jats:italic>B_His445Tyr, <jats:italic>inh<\/jats:italic>A\u201015(C\u2010T) and <jats:italic>rrs_<\/jats:italic>A1401G. Multidrug\u2010resistant strains (19.5%) harboured compensatory mutations linked to rifampicin resistance in <jats:italic>rpo<\/jats:italic>A, <jats:italic>rpo<\/jats:italic>B, or <jats:italic>rpo<\/jats:italic>C. Notably, the frequency of compensatory mutations in Beijing genotypes was significantly higher than in East African\u2013Indian genotypes (21.1% vs. 3.3%, OR\u2009=\u20097.7; 95% CI\u2009=\u20091.0 to 61.2, <jats:italic>p<\/jats:italic>\u2009=\u20090.03). The proportion of multidrug\u2010resistant strains with <jats:italic>rpo<\/jats:italic>B_Ser450Leu mutations carrying <jats:italic>rpo<\/jats:italic>A\u2013<jats:italic>rpo<\/jats:italic>C mutations was higher than that of strains with other <jats:italic>rpo<\/jats:italic>B mutations (OR\u2009=\u20095.4; 95% CI\u2009=\u20091.4 to 21.1, <jats:italic>p<\/jats:italic>\u2009=\u20090.02) and was associated with Beijing strains. Only 1.2% (2\/170) isoniazid\u2010resistant strains carried <jats:italic>aph<\/jats:italic>C\u201052(C\u2010T) mutation in the promoter region of the <jats:italic>ahp<\/jats:italic>C gene, which was hypothesised to be the compensatory mutation in isoniazid\u2010resistant strains. Meanwhile, 11 isoniazid\u2010resistant strains carried a <jats:italic>kat<\/jats:italic>G mutation combined with either <jats:italic>inh<\/jats:italic>A\u20108(T\u2010C) or <jats:italic>inh<\/jats:italic>A\u201015(A\u2010T) mutations and were associated with East African\u2013Indian strains.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mutations associated with high levels of drug resistance without\/with low fitness costs (<jats:italic>rpo<\/jats:italic>B_Ser450Leu and <jats:italic>kat<\/jats:italic>G_Ser315Thr) along with compensatory mutations linked to rifampicin resistance were strongly associated with multidrug\u2010resistant <jats:italic>M. tuberculosis<\/jats:italic> Beijing strains in Vietnam.<\/jats:p><\/jats:sec>","DOI":"10.1111\/tmi.14104","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T07:23:26Z","timestamp":1741850606000},"page":"426-436","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Multi\u2010drug resistance and compensatory mutations in <i>Mycobacterium tuberculosis<\/i> in Vietnam"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3452-1811","authenticated-orcid":false,"given":"Quang Huy","family":"Nguyen","sequence":"first","affiliation":[{"name":"LMI DRISA, Department of Life Sciences University of Science and Technology of Hanoi (USTH), Vietnam Academy of Science and Technology (VAST)  Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thi Van Anh","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Bacteriology National Institute of Hygiene and Epidemiology (NIHE)  Hanoi Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne\u2010Laure","family":"Ba\u00f1uls","sequence":"additional","affiliation":[{"name":"LMI DRISA, Department of Life Sciences University of Science and Technology of Hanoi (USTH), Vietnam Academy of Science and Technology (VAST)  Hanoi Vietnam"},{"name":"MIVEGEC University of Montpellier, IRD, CNRS  Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,13]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"WHO.Global tuberculosis report 2023. 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