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In the Western Cape, South Africa, co-infection of tuberculosis and HIV is a significant public health concern contributing to a higher burden of disease.\u00a0We compared the transcriptomes of two genetically similar Beijing family strains of\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    under four different growth conditions, including oxidative stress, using three biological replicates for each isolate.\u00a0We identified an operon containing genes involved in the biosynthesis of molybdenum cofactor that showed consistently lower levels of expression in the hypervirulent isolate. This pathway is known to play a critical role in numerous metabolic and redox processes, and its dysregulation could contribute to the observed differences in disease severity between the two isolates. The\n                    <jats:italic>moa<\/jats:italic>\n                    genes, which are involved in the biosynthesis of the molybdenum cofactor, have been previously linked to\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    virulence through their essential role in redox metabolism and oxidative stress response.\u00a0Our results support this hypothesis by identifying differential expression of the\n                    <jats:italic>moa<\/jats:italic>\n                    operon as a potential mechanism underlying the differences in disease severity between the two isolates. Furthermore, the minimal genetic differences between these isolates make them an ideal system for further study of this pathway and its contributions to tuberculosis pathogenesis.\n                  <\/jats:p>","DOI":"10.1007\/s00284-026-05038-2","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:37:59Z","timestamp":1785173879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional Profiling of Hypo- and Hypervirulent Mycobacterium tuberculosis Isolates Characterised by Differential Expression of the Moa3 Operon"],"prefix":"10.1007","volume":"83","author":[{"given":"Jon Mitchell","family":"Ambler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthys Gerhardus","family":"Potgieter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Klopper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Grobbelaar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaretha","family":"De Vos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Sampson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Mark Warren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Blackburn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4905-0941","authenticated-orcid":false,"given":"Nicola","family":"Mulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"issue":"3","key":"5038_CR1","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/path.2055","volume":"210","author":"S Aly","year":"2006","unstructured":"Aly S, Wagner K, Keller C (2006) Oxygen status of lung granulomas in Mycobacterium tuberculosis-infected mice. 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