Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis

Yang Luo, Chuan Chin Huang, Nicole C. Howard, Xin Wang, Qingyun Liu, Xinyi Li, Junhao Zhu, Tiffany Amariuta, Samira Asgari, Kazuyoshi Ishigaki, Roger Calderon, Sahadevan Raman, Alexandrea K. Ramnarine, Jacob A. Mayfield, D. Branch Moody, Leonid Lecca, Sarah M. Fortune, Megan B. Murray, Soumya Raychaudhuri

Research output: Contribution to journalArticlepeer-review

Abstract

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 languageEnglish
Article number10393
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

Fingerprint

Dive into the research topics of 'Paired analysis of host and pathogen genomes identifies determinants of human tuberculosis'. Together they form a unique fingerprint.

Cite this