{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T15:15:05Z","timestamp":1789398905942,"version":"build-2803163510"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"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. Microbiol."],"abstract":"\n Introduction<\/jats:title>\n \n We aimed to investigate the clinical significance and in-host evolution of\n Mycobacterium septicum<\/jats:italic>\n and\n Mycolicibacterium nivoides<\/jats:italic>\n , two closely-related nontuberculous mycobacteria.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Using a detailed single-case study, we investigated pulmonary co-infection of\n M. septicum<\/jats:italic>\n and\n M. nivoides<\/jats:italic>\n by examining clinical data, conducting microbiological assays, performing genome sequencing for 20 colonies from each sample, and evaluating virulence using\n Galleria mellonella<\/jats:italic>\n larva. We conducted a literature review to summarize\n M. septicum<\/jats:italic>\n and\n M. nivoides<\/jats:italic>\n clinical cases and curated all publicly-accessible genomes.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the pulmonary co-infection, both\n M. septicum<\/jats:italic>\n and\n M. nivoides<\/jats:italic>\n were implicated as the causative agents and exhibited remarkable intra-strain genomic heterogeneity. We uncovered different putative in-host microevolution trajectories, via either\n \u03b1<\/jats:italic>\n \/\n \u03b2<\/jats:italic>\n hydrolase variation for\n M. septicum<\/jats:italic>\n or\n papA2<\/jats:italic>\n (trehalose-2-sulfate acyltransferase-encoding gene) mutation for\n M. nivoides<\/jats:italic>\n . Intriguingly, both mutations were associated with enhanced virulence in the\n G. mellonella<\/jats:italic>\n model. We identified 19 additional cases with\n M. septicum<\/jats:italic>\n in literature, showing its multiple roles as a pathogen, a colonizer, or a contaminant. Re-analysis of 16 publicly-accessible genomes revealed misclassification of\n M. nivoides<\/jats:italic>\n , potentially underestimating its clinical significance.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n This study presents the first genomic evidence of co-infection of\n M. septicum<\/jats:italic>\n and\n M. nivoides<\/jats:italic>\n and divergent putative within-host evolution in a human patient. Simultaneously identifying multiple NTM colonies in chronic infection is needed for precise diagnosis. The observed convergence towards increased model virulence warrants further investigation as a potential adaptive strategy in NTM.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1791000","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T05:33:55Z","timestamp":1775540035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical significance and simultaneous microevolution of two closely-related nontuberculous mycobacteria species"],"prefix":"10.3389","volume":"17","author":[{"given":"Chengcheng","family":"Wang","sequence":"first","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Pathogen Research, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feifei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"McNally","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Infection, College of Medicine and Health, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Zong","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy","place":["Chengdu, China"]},{"name":"Laboratory of Pathogen Research, West China Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"State Key Laboratory of Respiratory Health and Multimorbidity","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1099\/ijs.0.63094-0","article-title":"Dissection of phylogenetic relationships among 19 rapidly growing Mycobacterium species by 16S rRNA, hsp65, sodA, recA and rpoB gene sequencing","volume":"54","author":"Ad\u00e9kambi","year":"2004","journal-title":"Int. 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