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Dependency on host vitamin B12 has shaped Mycobacterium tuberculosis Complex evolution

Human and animal tuberculosis is caused by the Mycobacterium tuberculosis Complex (MTBC), which has evolved a genomic decay of cobalamin (vitamin B12) biosynthetic genes. Accordingly, and in sharp contrast to environmental, opportunistic and ancestor mycobacteria; we demonstrate that M. tuberculosis...

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Published in:Nature communications 2024-03, Vol.15 (1), p.2161-2161, Article 2161
Main Authors: Campos-Pardos, Elena, Uranga, Santiago, Picó, Ana, Gómez, Ana Belén, Gonzalo-Asensio, Jesús
Format: Article
Language:English
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Summary:Human and animal tuberculosis is caused by the Mycobacterium tuberculosis Complex (MTBC), which has evolved a genomic decay of cobalamin (vitamin B12) biosynthetic genes. Accordingly, and in sharp contrast to environmental, opportunistic and ancestor mycobacteria; we demonstrate that M. tuberculosis ( Mtb ), M. africanum , and animal-adapted lineages, lack endogenous production of cobalamin, yet they retain the capacity for exogenous uptake. A B12 anemic model in immunocompromised and immunocompetent mice, demonstrates improved survival, and lower bacteria in organs, in B12 anemic animals infected with Mtb relative to non-anemic controls. Conversely, no differences were observed between mice groups infected with M. canettii , an ancestor mycobacterium which retains cobalamin biosynthesis. Interrogation of the B12 transcriptome in three MTBC strains defined L-methionine synthesis by metE and metH genes as a key phenotype. Expression of metE is repressed by a cobalamin riboswitch, while MetH requires the cobalamin cofactor. Thus, deletion of metE predominantly attenuates Mtb in anemic mice; although inactivation of metH exclusively causes attenuation in non-anemic controls. Here, we show how sub-physiological levels of B12 in the host antagonizes Mtb virulence, and describe a yet unknown mechanism of host-pathogen cross-talk with implications for B12 anemic populations. Campos-Pardos et al show that the virulence of Mycobacterium tuberculosis is dependent on sufficient uptake of exogenous vitamin B12 from host serum and this phenotype is not conserved in environmental, opportunistic and ancestral lineages.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-46449-8