ArticlePLoS pathogens2017
Horizontal acquisition of a hypoxia-responsive molybdenum cofactor biosynthesis pathway contributed to Mycobacterium tuberculosis pathoadaptation.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 44 citations in OpenAlex.
- Transcriptional Profiling of Hypo- and Hypervirulent Mycobacterium tuberculosis Isolates Characterised by Differential Expression of the Moa3 Operon.Current microbiology · 2026Article
- Longitudinal gut microbiota tracking reveals the dynamics of horizontal gene transfer.Nature communications · 2025Article
- Inorganic sulfate is critical forProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Interred mechanisms of resistance and host immune evasion revealed through network-connectivity analysis ofmSystems · 2025Article
- Mycobacteria that cause tuberculosis have retained ancestrally acquired genes for the biosynthesis of chemically diverse terpene nucleosides.PLoS biology · 2024Article
- Unraveling bacterial stress responses: implications for next-generation antimicrobial solutions.World journal of microbiology & biotechnology · 2024Article
- [Construction and characterization of aNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- The efflux pumps Rv1877 and Rv0191 play differential roles in the protection ofFrontiers in microbiology · 2024Article
- Exposure ofFrontiers in tuberculosis · 2024Article
- The risk of pulmonary NTM infections and water-quality constituents among persons with cystic fibrosis in the United States, 2010-2019.Environmental epidemiology (Philadelphia, Pa.) · 2023Article
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- The molybdate-binding protein ModA is required forFrontiers in microbiology · 2023Article
- Mycobacterial resistance to zinc poisoning requires assembly of P-ATPase-containing membrane metal efflux platforms.Nature communications · 2022Article
- Resolving the Multidecade-Long Mystery in MoaA Radical SAM Enzyme Reveals New Opportunities to Tackle Human Health Problems.ACS bio & med chem Au · 2022Review
- Nontuberculous Mycobacteria Infection Risk and Trace Metals in Surface Water: A Population-based Ecologic Epidemiologic Study in Oregon.Annals of the American Thoracic Society · 2022Article
- Commonalities ofFrontiers in immunology · 2022Article
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- Nontuberculous Mycobacterial Disease and Molybdenum in Colorado Watersheds.International journal of environmental research and public health · 2020Article
- Multi-Stress Induction of theToxins · 2020Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The unique ability of the tuberculosis (TB) bacillus, Mycobacterium tuberculosis, to persist for long periods of time in lung hypoxic lesions chiefly contributes to the global burden of latent TB. We and others previously reported that the M. tuberculosis ancestor underwent massive episodes of horizontal gene transfer (HGT), mostly from environmental species. Here, we sought to explore whether such ancient HGT played a part in M. tuberculosis evolution towards pathogenicity. We were interested by a HGT-acquired M. tuberculosis-specific gene set, namely moaA1-D1, which is involved in the biosynthesis of the molybdenum cofactor. Horizontal acquisition of this gene set was striking because homologues of these moa genes are present all across the Mycobacterium genus, including in M. tuberculosis. Here, we discovered that, unlike their paralogues, the moaA1-D1 genes are strongly induced under hypoxia. In vitro, a M. tuberculosis moaA1-D1-null mutant has an impaired ability to respire nitrate, to enter dormancy and to survive in oxygen-limiting conditions. Conversely, heterologous expression of moaA1-D1 in the phylogenetically closest non-TB mycobacterium, Mycobacterium kansasii, which lacks these genes, improves its capacity to respire nitrate and grants it with a marked ability to survive oxygen depletion. In vivo, the M. tuberculosis moaA1-D1-null mutant shows impaired survival in hypoxic granulomas in C3HeB/FeJ mice, but not in normoxic lesions in C57BL/6 animals. Collectively, our results identify a novel pathway required for M. tuberculosis resistance to host-imposed stress, namely hypoxia, and provide evidence that ancient HGT bolstered M. tuberculosis evolution from an environmental species towards a pervasive human-adapted pathogen.
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