{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:10:47Z","timestamp":1779253847121,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background<\/jats:title>\n \n The regulatory mechanism of respiratory chain in\n Mycobacterium tuberculosis<\/jats:italic>\n (\n M. tuberculosis<\/jats:italic>\n ) remains to be elucidated, and limited evidence about the effect of gene mutations in the respiratory chain on multidrug-resistant (MDR) isolates was reported.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To elucidated the effect of gene mutations in the respiratory chain on MDR isolates.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Whole-genome sequencing was performed on analyzed strains of\n M. tuberculosis<\/jats:italic>\n . Random forest, gradient boosting decision tree and generalized linear mixed models were employed to identify mutations in respiratory chain genes that contribute to the phylogenetic clustering and development of MDR isolates.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Overall, a total of 13402 isolates of\n M. tuberculosis<\/jats:italic>\n were included in the study. 4051 (30.09%) isolates showed MDR, and 1044 (7.76%) isolates were classified as single\u2010drug resistance (SDR). The results showed that the single nucleotide polymorphisms (SNPs) of\n atpH<\/jats:italic>\n A428G,\n cydA<\/jats:italic>\n C942A,\n qcrA<\/jats:italic>\n G181C,\n nuoF<\/jats:italic>\n G66C,\n qcrB<\/jats:italic>\n G1250T,\n nuoA<\/jats:italic>\n G82C, and\n nuoG<\/jats:italic>\n A1422G A1810G were significantly associated with phylogenetic clustering of MDR isolates. The SNPs of\n ndhA<\/jats:italic>\n G1000A,\n atpH<\/jats:italic>\n C73G A428G,\n cydA<\/jats:italic>\n C942A,\n qcrA<\/jats:italic>\n G181C,\n qcrB<\/jats:italic>\n G55A,\n nuoG<\/jats:italic>\n A1422G,\n nuoJ<\/jats:italic>\n G115A,\n nuoN<\/jats:italic>\n G1084T,\n cydB<\/jats:italic>\n T126C,\n nuoA<\/jats:italic>\n G82C,\n nuoB<\/jats:italic>\n G490C,\n nuoF<\/jats:italic>\n C171T, and\n nuoK<\/jats:italic>\n C73T were significantly associated with formation of MDR isolates.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Our study proposed that SNPs in genes of the respiratory chain were related to the phylogenetic clustering and development of MDR isolates, which provides new insights for preventing the phylogenetic clustering and development of MDR isolates. These insights provide valuable information for the development of potential therapeutic targets for MDR isolates.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1724194","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T04:45:39Z","timestamp":1779252339000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Respiratory chain gene mutations associated with global phylogenetic clustering of drug-resistant Mycobacterium tuberculosis revealed by whole-genome sequencing"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiang","family":"Ji","sequence":"first","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yawei","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Qilu Second Hospital of Shandong University","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yameng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Shandong First Medical University (Affiliated Hospital of Shandong Academy of Medical Sciences)","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.589318","article-title":"Terminal respiratory oxidases: A targetables vulnerability of mycobacterial bioenergetics","volume":"10","author":"Bajeli","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1086\/590009","article-title":"Extensively drug-resistant tuberculosis in california, 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