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Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.06, 95%CI: 4.87 - 20.77, P = 7.92 × 10-8) in the FLOT1 gene and a subclavaluee of Mtb Lineage 2. In a human macrophage infection model, we observe hosts with the rs3130660-A allele exhibited stronger interferon gene signatures. The interacting strains have altered redox states due to a thioredoxin reductase mutation. We investigate this association in a 2020 cohort of 699 patients recruited during the COVID-19 pandemic. While the prevalence of the interacting strain almost doubled between 2010 and 2020, its infection is not associated with rs3130660 in this recent cohort. These findings suggest a complex interplay among host, pathogen, and environmental factors in tuberculosis dynamics.

Original publication

DOI

10.1038/s41467-024-54741-w

Type

Journal article

Journal

Nat commun

Publication Date

29/11/2024

Volume

15

Keywords

Humans, Mycobacterium tuberculosis, Tuberculosis, Peru, Host-Pathogen Interactions, Genome, Bacterial, COVID-19, Macrophages, Female, Polymorphism, Single Nucleotide, Male, Cohort Studies, Mutation, Adult, Thioredoxin-Disulfide Reductase, SARS-CoV-2